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The cilium, plural cilia (), is a
membrane-bound organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...
found on most types of eukaryotic
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
, and certain microorganisms known as
ciliate The ciliates are a group of alveolates characterized by the presence of hair-like organelles called cilia, which are identical in structure to eukaryotic flagella, but are in general shorter and present in much larger numbers, with a differen ...
s. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projection that extends from the surface of the much larger
cell body The soma (pl. ''somata'' or ''somas''), perikaryon (pl. ''perikarya''), neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. The word 'soma' comes from the Greek '' σῶμ ...
. Eukaryotic flagella found on sperm cells and many protozoans have a similar structure to motile cilia that enables swimming through liquids; they are longer than cilia and have a different undulating motion. There are two major classes of cilia: ''motile'' and ''non-motile'' cilia, each with a subtype, giving four types in all. A cell will typically have one primary cilium or many motile cilia. The structure of the cilium core called the
axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme ...
determines the cilium class. Most motile cilia have a central pair of single microtubules surrounded by nine pairs of double microtubules called a
9+2 axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme ...
. Most non-motile cilia have a
9+0 axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme ...
that lacks the central pair of microtubules. Also lacking are the associated components that enable motility including the outer and inner dynein arms, and radial spokes. Some motile cilia lack the central pair, and some non-motile cilia have the central pair, hence the four types. Most non-motile cilia are termed ''primary cilia'' or ''sensory cilia'' and serve solely as sensory organelles. Most vertebrate cell types possess a single non-motile primary cilium, which functions as a cellular antenna.
Olfactory neuron An olfactory receptor neuron (ORN), also called an olfactory sensory neuron (OSN), is a sensory neuron within the olfactory system. Structure Humans have between 10 and 20 million olfactory receptor neurons (ORNs). In vertebrates, ORNs are b ...
s possess a great many non-motile cilia. Non-motile cilia that have a central pair of microtubules are the
kinocilia A kinocilium is a special type of cilium on the apex of hair cells located in the sensory epithelium of the vertebrate inner ear. Anatomy in humans Kinocilia are found on the apical surface of hair cells and are involved in both the morphogenesis ...
present on
hair cell Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates, and in the lateral line organ of fishes. Through mechanotransduction, hair cells detect movement in their environment. ...
s. Motile cilia are found in large numbers on respiratory epithelial cells – around 200 cilia per cell, where they function in mucociliary clearance, and also have mechanosensory and
chemosensory A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal. This signal may be in the form of an action potential, if the chemorecept ...
functions. Motile cilia on ependymal cells move the
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the b ...
through the
ventricular system The ventricular system is a set of four interconnected cavities known as cerebral ventricles in the brain. Within each ventricle is a region of choroid plexus which produces the circulating cerebrospinal fluid (CSF). The ventricular system is co ...
of the brain. Motile cilia are also present in the fallopian tubes of female mammals where they function in moving the
egg cell The egg cell, or ovum (plural ova), is the female reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female gamete is ...
from the
ovary The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
to the uterus. Motile cilia that lack the central pair of microtubules are the cells of the embryonic
primitive node The primitive node (or primitive knot) is the organizer for gastrulation in most amniote embryos. In birds it is known as Hensen's node, and in amphibians it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in a ...
termed ''nodal cells'' and these nodal cilia are responsible for the
left-right asymmetry Left-right asymmetry, (LR asymmetry) is the process in early embryonic development that breaks the normal symmetry in the bilateral embryo. In vertebrates, left-right asymmetry is established early in development at a structure called the left-r ...
in
bilateral animals The Bilateria or bilaterians are animals with bilateral symmetry as an embryo, i.e. having a left and a right side that are mirror images of each other. This also means they have a head and a tail (anterior-posterior axis) as well as a belly and ...
.


Structure

A cilium is assembled and built from a
basal body A basal body (synonymous with basal granule, kinetosome, and in older cytological literature with blepharoplast) is a protein structure found at the base of a eukaryotic undulipodium (cilium or flagellum). The basal body was named by Theodor W ...
on the cell surface. From the basal body the ciliary rootlet forms ahead of the transition plate and transition zone where the earlier microtubule triplets change to the microtubule doublets of the axoneme.


Basal body

The foundation of the cilium is the basal body, a term applied to the mother centriole when it is associated with a cilium. Mammalian basal bodies consist of a barrel of nine triplet microtubules, subdistal appendages and nine strut-like structures, known as distal appendages, which attach the basal body to the membrane at the base of the cilium. Two of each of the basal body's triplet microtubules extend during growth of the axoneme to become the doublet microtubules.


Ciliary rootlet

The ciliary rootlet is a cytoskeleton-like structure that originates from the basal body at the proximal end of a cilium. Rootlets are typically 80-100 nm in diameter and contain cross striae distributed at regular intervals of approximately 55-70 nm. A prominent component of the rootlet is rootletin a coiled coil rootlet protein coded for by the ''CROCC'' gene.


Transition zone

To achieve its distinct composition, the proximal-most region of the cilium consists of a transition zone, also known as the ciliary gate, that controls the entry and exit of proteins to and from the cilium. At the transition zone, Y-shaped structures connect the ciliary membrane to the underlying axoneme. Control of selective entry into cilia may involve a sieve-like function of transition zone. Inherited defects in components of the transition zone cause ciliopathies, such as Joubert syndrome. Transition zone structure and function is conserved across diverse organisms, including vertebrates, ''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...
'', '' Drosophila melanogaster'' and ''
Chlamydomonas reinhardtii ''Chlamydomonas reinhardtii'' is a single-cell green alga about 10 micrometres in diameter that swims with two flagella. It has a cell wall made of hydroxyproline-rich glycoproteins, a large cup-shaped chloroplast, a large pyrenoid, and an eyes ...
''. In mammals, disruption of the transition zone reduces the ciliary abundance of membrane-associated ciliary proteins, such as those involved in Hedgehog signal transduction, compromising Hedgehog-dependent embryonic development of digit number and central nervous system patterning.


Axoneme

Inside a cilium, is a microtubule-based cytoskeletal core called the
axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme ...
. The axoneme of a primary cilium typically has a ring of nine outer microtubule doublets (called a
9+0 axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme ...
), and the axoneme of a motile cilium has, in addition to the nine outer doublets, two central microtubule singlets (called a
9+2 axoneme An axoneme, also called an axial filament is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to provide motility. The axoneme ...
). This is the same axoneme type of the flagellum. The axoneme in a motile cilium acts as a scaffold for the inner and outer dynein arms that move the cilium, and provides tracks for the microtubule motor proteins of kinesin and dynein. The transport of ciliary components is carried out by intraflagellar transport (IFT) which is similar to the
axonal transport Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytoplas ...
in a nerve fibre. Transport is bidirectional and cytoskeletal motor proteins kinesin and dynein transport ciliary components along the microtubule tracks; kinesin in an anterograde movement towards the ciliary tip and dynein in a retrograde movement towards the cell body. The cilium has its own ciliary membrane enclosed within the surrounding cell membrane.


Types


Non-motile cilia

In animals, non-motile primary cilia are found on nearly every type of cell, blood cells being a prominent exception. Most cells only possess one, in contrast to cells with motile cilia, an exception being olfactory sensory neurons, where the
odorant receptors Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give r ...
are located, which each possess about ten cilia. Some cell types, such as retinal photoreceptor cells, possess highly specialized primary cilia. Although the primary cilium was discovered in 1898, it was largely ignored for a century and considered a vestigial organelle without important function. Recent findings regarding its physiological roles in chemosensation, signal transduction, and cell growth control, have revealed its importance in cell function. Its importance to human biology has been underscored by the discovery of its role in a diverse group of diseases caused by the dysgenesis or dysfunction of cilia, such as polycystic kidney disease,
congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
,
mitral valve prolapse Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. It is the primary form of myxomatous degeneration of the valve. There ar ...
, and retinal degeneration, called
ciliopathies A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while ...
. The primary cilium is now known to play an important role in the function of many human organs. Primary cilia on pancreatic
beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
s regulate their function and energy metabolism. Cilia deletion can lead to islet dysfunction and type 2 diabetes. Cilia are assembled during the G1 phase and are disassembled before mitosis occurs. Disassembly of cilia requires the action of aurora kinase A. The current scientific understanding of primary cilia views them as "sensory cellular antennae that coordinate many cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation." The cilium is composed of subdomains and enclosed by a plasma membrane continuous with the plasma membrane of the cell. For many cilia, the
basal body A basal body (synonymous with basal granule, kinetosome, and in older cytological literature with blepharoplast) is a protein structure found at the base of a eukaryotic undulipodium (cilium or flagellum). The basal body was named by Theodor W ...
, where the cilium originates, is located within a membrane invagination called the ciliary pocket. The cilium membrane and the basal body microtubules are connected by distal appendages (also called transition fibers). Vesicles carrying molecules for the cilia dock at the distal appendages. Distal to the transition fibers form a transition zone where entry and exit of molecules is regulated to and from the cilia. Some of the signaling with these cilia occur through ligand binding such as Hedgehog signaling. Other forms of signaling include G protein-coupled receptors including the
somatostatin receptor 3 Shekel Somatostatin receptor type 3 is a protein that in humans is encoded by the ''SSTR3'' gene. Function Somatostatin acts at many sites to inhibit the release of many hormones and other secretory proteins. The biological effects of somato ...
in neurons.


Modified non-motile cilia

Kinocilia A kinocilium is a special type of cilium on the apex of hair cells located in the sensory epithelium of the vertebrate inner ear. Anatomy in humans Kinocilia are found on the apical surface of hair cells and are involved in both the morphogenesis ...
that are found on hair cells in the inner ear are termed as specialized primary cilia, or modified non-motile cilia. They possess the 9+2 axoneme of the motile cilia but lack the inner dynein arms that give movement. They do move passively following the detection of sound, allowed by the outer dynein arms.


Motile cilia

Mammals also have motile cilia or secondary cilia that are usually present on a cell's surface in large numbers (multiciliate), and beat in coordinated metachronal waves. Multiciliated cells are found lining the respiratory tract where they function in mucociliary clearance sweeping mucus containing debris away from the lungs. Each cell in the respiratory epithelium has around 200 motile cilia. In the
reproductive tract The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are al ...
, smooth muscle contractions help the beating of the cilia in moving the
egg cell The egg cell, or ovum (plural ova), is the female reproductive cell, or gamete, in most anisogamous organisms (organisms that reproduce sexually with a larger, female gamete and a smaller, male one). The term is used when the female gamete is ...
from the ovary to the uterus. In the ventricles of the brain ciliated ependymal cells circulate the
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the b ...
. The functioning of motile cilia is strongly dependent on the maintenance of optimal levels of periciliary fluid bathing the cilia.
Epithelial sodium channel The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α ...
s (ENaCs) are specifically expressed along the entire length of cilia in the respiratory tract, and Fallopian tube or ''oviduct'' that apparently serve as sensors to regulate the periciliary fluid.


Modified motile cilia

Motile cilia without the central pair of singlets (9+0) are found in early embryonic development. They are present as nodal cilia on the nodal cells of the
primitive node The primitive node (or primitive knot) is the organizer for gastrulation in most amniote embryos. In birds it is known as Hensen's node, and in amphibians it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in a ...
. Nodal cells are responsible for the
left-right asymmetry Left-right asymmetry, (LR asymmetry) is the process in early embryonic development that breaks the normal symmetry in the bilateral embryo. In vertebrates, left-right asymmetry is established early in development at a structure called the left-r ...
in
bilateral animals The Bilateria or bilaterians are animals with bilateral symmetry as an embryo, i.e. having a left and a right side that are mirror images of each other. This also means they have a head and a tail (anterior-posterior axis) as well as a belly and ...
. While lacking the central apparatus there are dynein arms present that allow the nodal cilia to move in a spinning fashion. The movement creates a current flow of the extraembryonic fluid across the nodal surface in a leftward direction that initiates the left-right asymmetry in the developing embryo. Motile, multiple, 9+0 cilia are found on the epithelial cells of the
choroid plexus The choroid plexus, or plica choroidea, is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain. Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central nervo ...
. Cilia also can change structure when introduced to hot temperatures and become sharp. They are present in large numbers on each cell and move relatively slowly, making them intermediate between motile and primary cilia. In addition to 9+0 cilia that are mobile, there are also solitary 9+2 cilia that stay immobile found in hair cells.


Nodal cilia

Nodal cells have a single cilium called a monocilium. They are present in the very early development of the embryo on the
primitive node The primitive node (or primitive knot) is the organizer for gastrulation in most amniote embryos. In birds it is known as Hensen's node, and in amphibians it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in a ...
. There are two areas of the node with different types of nodal cilia. On the central node are motile cilia, and on the peripheral area of the node the nodal cilia are modified motile. The motile cilia on the central cells rotate to generate the leftward flow of extracellular fluid needed to initiate the left-right asymmetry.


Cilia versus flagella

The motile cilia on sperm cells and many protozoans enables swimming through liquids and are traditionally referred to as " flagella". As these protrusions are structurally identical to motile cilia, attempts at preserving this terminology include making a distinction by morphology ("flagella" are typically longer than ordinary cilia and have a different undulating motion) and by number.


Microorganisms

Ciliate The ciliates are a group of alveolates characterized by the presence of hair-like organelles called cilia, which are identical in structure to eukaryotic flagella, but are in general shorter and present in much larger numbers, with a differen ...
s are eukaryotic microorganisms that possess motile cilia exclusively and use them for either locomotion or to simply move liquid over their surface. A '' Paramecium'' for example is covered in thousands of cilia that enable its swimming. These motile cilia have been shown to be also sensory.


Ciliogenesis

Cilia are formed through the process of
ciliogenesis Ciliogenesis is defined as the building of the cell's antenna ( primary cilia) or extracellular fluid mediation mechanism ( motile cilium). It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important organe ...
. An early step is docking of the basal body to the growing ciliary membrane, after which the transition zone forms. The building blocks of the ciliary axoneme, such as
tubulins Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...
, are added at the ciliary tips through a process that depends partly on intraflagellar transport (IFT). Exceptions include ''Drosophila'' sperm and '' Plasmodium falciparum'' flagella formation, in which cilia assemble in the cytoplasm. At the base of the cilium where it attaches to the cell body is the
microtubule organizing center The microtubule-organizing center (MTOC) is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spi ...
, the
basal body A basal body (synonymous with basal granule, kinetosome, and in older cytological literature with blepharoplast) is a protein structure found at the base of a eukaryotic undulipodium (cilium or flagellum). The basal body was named by Theodor W ...
. Some basal body proteins as CEP164, ODF2 and CEP170, are required for the formation and the stability of the cilium. In effect, the cilium is a
nanomachine A molecular machine, nanite, or nanomachine is a molecular component that produces quasi-mechanical movements (output) in response to specific stimuli (input). In cellular biology, macromolecular machines frequently perform tasks essential for l ...
composed of perhaps over 600 proteins in molecular complexes, many of which also function independently as nanomachines.
Flexible linker In molecular biology, an intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure, typically in the absence of its macromolecular interaction partners, such as other proteins or RNA. IDPs ran ...
s allow the mobile protein domains connected by them to recruit their binding partners and induce long-range
allostery In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric site ...
via protein domain dynamics.


Function

The
dynein Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements important ...
in the axoneme –
axonemal dynein Dyneins are a family of cytoskeletal motor proteins that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargos, provides forces and displacements important ...
forms bridges between neighbouring microtubule doublets. When ATP activates the motor domain of dynein, it attempts to walk along the adjoining microtubule doublet. This would force the adjacent doublets to slide over one another if not for the presence of
nexin Nexin is a proteinous inter-doublet linkage that prevents microtubules in the outer layer of axonemes from moving with respect to one another; otherwise, vesicular transport proteins such as dynein would dissolve the whole structure. Page 26 See ...
between the microtubule doublets. And thus the force generated by dynein is instead converted into a bending motion.


Sensing the extracellular environment

Some primary cilia on
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
cells in eukaryotes act as ''cellular antennae'', providing chemosensation,
thermosensation Thermoception or thermoreception is the sensation and perception of temperature, or more accurately, temperature differences inferred from heat flux. It deals with a series of events and processes required for an organism to receive a temperature s ...
and mechanosensation of the extracellular environment. These cilia then play a role in mediating specific signalling cues, including soluble factors in the external cell environment, a secretory role in which a soluble protein is released to have an effect downstream of the fluid flow, and mediation of fluid flow if the cilia are
motile Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
. Some
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
cells are ciliated, and they commonly exist as a sheet of polarized cells forming a tube or tubule with cilia projecting into the lumen. This sensory and signalling role puts cilia in a central role for maintaining the local cellular environment and may be why ciliary defects cause such a wide range of human diseases. In the embryo, nodal cilia are used to direct the flow of extracellular fluid. This leftward movement is to generate
left-right asymmetry Left-right asymmetry, (LR asymmetry) is the process in early embryonic development that breaks the normal symmetry in the bilateral embryo. In vertebrates, left-right asymmetry is established early in development at a structure called the left-r ...
across the midline of the embryo. Central cilia coordinate their rotational beating while the immotile cilia on the sides sense the direction of the flow.


Axo-ciliary synapse

With axo-ciliary synapses, there is communication between serotonergic
axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
s and primary cilia of CA1 pyramidal neurons that alters the neuron's
epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
state in the
nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: * Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...
– "a way to change what is being transcribed or made in the nucleus" via this signalling distinct from that at the plasma membrane which also is longer-term.


Clinical significance

Ciliary defects can lead to a number of human diseases. Defects in cilia adversely affect many critical signaling pathways essential to embryonic development and to adult physiology, and thus offer a plausible hypothesis for the often multi-symptom nature of diverse ciliopathies. Known ciliopathies include
primary ciliary dyskinesia Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of sper ...
, Bardet–Biedl syndrome, polycystic kidney and
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...
, nephronophthisis,
Alström syndrome Alström syndrome (AS), also called Alström–Hallgren syndrome, is a very rare autosomal recessive genetic disorder characterised by childhood obesity and multiple organ dysfunction. Symptoms include early-onset type 2 diabetes, cone-rod dyst ...
,
Meckel–Gruber syndrome Meckel-Gruber syndrome is a rare, lethal ciliopathic genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (postaxial), hepatic developmental defects, and pulmonary h ...
,
Sensenbrenner syndrome Sensenbrenner syndrome (OMIM #218330) is a rare (less than 20 cases reported by 2010) multisystem disease first described by Judith A. Sensenbrenner in 1975. It is inherited in an autosomal recessive fashion, and a number of genes appear to be resp ...
and some forms of retinal degeneration. Genetic mutations compromising the proper functioning of cilia,
ciliopathies A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while ...
, can cause chronic disorders such as
primary ciliary dyskinesia Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of sper ...
(PCD), nephronophthisis, and Senior–Løken syndrome. In addition, a defect of the primary cilium in the
renal tubule The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure c ...
cells can lead to polycystic kidney disease (PKD). In another genetic disorder called Bardet–Biedl syndrome (BBS), the mutant gene products are the components in the basal body and cilia. Defects in cilia cells are linked to obesity and often pronounced in type 2 diabetes. Several studies already showed impaired glucose tolerance and reduction in the insulin secretion in the ciliopathy models. Moreover, the number and length of cilia was decreased in the type 2 diabetes models.
Epithelial sodium channels The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α ...
(ENaCs) that are expressed along the length of cilia regulate periciliary fluid level. Mutations that decrease the activity of ENaCs result in multisystem
pseudohypoaldosteronism Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of ''response'' to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition. Types P ...
, that is associated with fertility problems. In cystic fibrosis that results from mutations in the chloride channel
CFTR Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the ''CFTR'' gene. Geneticist Lap-Chee Tsui and his team identified the CFTR gene in 1989 as the gene linked wi ...
, ENaC activity is enhanced leading to a severe reduction of the fluid level that causes complications and infections in the respiratory airways. Since the flagellum of human sperm has the same internal structure of a cilium, ciliary dysfunction can also be responsible for male infertility. There is an association of primary ciliary dyskinesia with left-right anatomic abnormalities such as situs inversus (a combination of findings is known as
Kartagener syndrome Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of sper ...
), and
situs ambiguus Situs ambiguus is a rare congenital defect in which the major visceral organs are distributed abnormally within the chest and abdomen. Clinically heterotaxy spectrum generally refers to any defect of Left-right asymmetry and arrangement of the visc ...
(also known as ''Heterotaxy syndrome''). These left-right anatomic abnormalities can also result in
congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
. It has been shown that proper cilial function is responsible for the normal left-right asymmetry in mammals. The diverse outcomes caused by ciliary dysfunction may result from alleles of different strengths that compromise ciliary functions in different ways or to different extents. Many ciliopathies are inherited in a Mendelian manner, but specific genetic interactions between distinct functional ciliary complexes, such as transition zone and BBS complexes, can alter the phenotypic manifestations of recessive ciliopathies. Some mutations in transition zone proteins can cause specific serious ciliopathies.


Extracellular changes

Reduction of cilia function can also result from infection. Research into
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular p ...
s has shown that bacteria can alter cilia. A biofilm is a community of bacteria of either the same or multiple species of bacteria. The cluster of cells secretes different factors which form an extracellular matrix. Cilia in the respiratory system is known to move mucus and pathogens out of the airways. It has been found that patients with biofilm positive infections have impaired cilia function. The impairment may present as decreased motion or reduction in the number of cilia. Though these changes result from an external source, they still effect the pathogenicity of the bacteria, progression of infection, and how it is treated. The transportation of the immature egg cell, and the embryo to the uterus for implantation depends on the combination of regulated smooth muscle contractions, and ciliary beating. Dysfunction in this transportation can result in an
ectopic pregnancy Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. ...
where the embryo is implanted (usually) in the Fallopian tube before reaching its proper destination of the uterus. Many factors can affect this stage including infection and menstrual cycle hormones. Smoking (causing inflammation), and infection can reduce the numbers of cilia, and the ciliary beat can be affected by hormonal changes.


Primary cilia in pancreatic cells

The pancreas is a mixture of highly differentiated exocrine and endocrine cells. Primary cilia are present in exocrine cells which are centroacinar, duct cells. Endocrine tissue is composed of different hormone secreting cells. Insulin secreting beta cells and glucagon secreting alpha cells which are highly ciliated.Yamamoto M, Kataoka K. 1986. Electron microscopic observation of the primary cilia in the pancreatic islets. Arch Histol Jpn 49: 449–457


See also

* Biological machines * Protein domain dynamics * Protein flexibility *
Stereocilia Stereocilia (or stereovilli or villi) are non-motile apical cell modifications. They are distinct from cilia and microvilli, but are closely related to microvilli. They form single "finger-like" projections that may be branched, with normal cell ...


References


External links


Brief summary of importance of cilia to many organs in human physiology

The Ciliary Proteome Web Page at Johns Hopkins
{{Authority control Cell movement Organelles