Cell polarity refers to spatial differences in shape, structure, and function within a
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 ...
. Almost all cell types exhibit some form of polarity, which enables them to carry out specialized functions. Classical examples of polarized cells are described below, including epithelial cells with apical-basal polarity,
neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s in which signals propagate in one direction from
dendrite
Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...
s to
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 po ...
s, and
migrating cells. Furthermore, cell polarity is important during many types of
asymmetric cell division
An asymmetric cell division produces two daughter cells with different cellular fates. This is in contrast to symmetric cell divisions which give rise to daughter cells of equivalent fates. Notably, stem cells divide asymmetrically to give rise to ...
to set up functional asymmetries between daughter cells.
Many of the key molecular players implicated in cell polarity are well conserved. For example, in
metazoan
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
cells, the PAR-3/PAR-6/aPKC complex plays a fundamental role in cell polarity. While the biochemical details may vary, some of the core principles such as negative and/or positive feedback between different molecules are common and essential to many known polarity systems.
Examples of polarized cells
Epithelial cells
Epithelial cells adhere to one another through
tight junctions
Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...
,
desmosome
A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...
s and
adherens junctions
Adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions, cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. ...
, forming sheets of cells that line the surface of the animal body and internal cavities (e.g., digestive tract and circulatory system). These cells have an apical-basal polarity defined by the
apical membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
facing the outside surface of the body, or the
lumen of internal cavities, and the
basolateral membrane Epithelial polarity is one example of the cell polarity that is a fundamental feature of many types of cells. Epithelial cells feature distinct 'apical', 'lateral' and 'basal' plasma membrane domains. Epithelial cells connect to one another via t ...
oriented away from the lumen. The basolateral membrane refers to both the lateral membrane where cell-cell junctions connect neighboring cells and to the basal membrane where cells are attached to the
basement membrane
The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...
, a thin sheet of
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide stru ...
proteins that separates the epithelial sheet from underlying cells and
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
. Epithelial cells also exhibit planar cell polarity, in which specialized structures are orientated within the plane of the epithelial sheet. Some examples of planar cell polarity include the scales of fish being oriented in the same direction and similarly the feathers of birds, the fur of mammals, and the cuticular projections (sensory hairs, etc.) on the bodies and appendages of flies and other insects. Computational models have been suggested to simulate how a group of epithelial cells can form a variety of biological morphologies.
Neurons
A neuron receives signals from neighboring cells through branched, cellular extensions called
dendrites
Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the n ...
. The neuron then propagates an electrical signal down a specialized
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 po ...
extension from the basal pole to the synapse, where neurotransmitters are released to propagate the signal to another neuron or effector cell (e.g., muscle or gland). The polarity of the neuron thus facilitates the directional flow of information, which is required for communication between neurons and effector cells.
Migratory cells
Many cell types are capable of migration, such as
leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
and
fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...
, and in order for these cells to move in one direction, they must have a defined front and rear. At the front of the cell is the leading edge, which is often defined by a flat ruffling of the cell membrane called the
lamellipodium
The lamellipodium (plural lamellipodia) (from Latin ''lamella'', related to ', "thin sheet", and the Greek radical ''pod-'', "foot") is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional ...
or thin protrusions called
filopodia
Filopodia (singular filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as ''microspikes'', and when they extend beyond the lame ...
. Here,
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
polymerization in the direction of migration allows cells to extend the leading edge of the cell and to attach to the surface. At the rear of the cell, adhesions are disassembled and bundles of actin
microfilaments
Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other pr ...
, called
stress fiber
Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin II (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated ...
s, contract and pull the trailing edge forward to keep up with the rest of the cell. Without this front-rear polarity, cells would be unable to coordinate directed migration.
Budding yeast
The budding yeast, ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'', is a model system for eukaryotic biology in which many of the fundamental elements of polarity development have been elucidated. Yeast cells share many features of cell polarity with other organisms, but feature fewer protein components. In yeast, polarity is biased to form at an inherited landmark, a patch of the protein Rsr1 in the case of budding, or a patch of Rax1 in mating projections. In the absence of polarity landmarks (i.e. in gene deletion mutants), cells can perform spontaneous
symmetry breaking
In physics, symmetry breaking is a phenomenon in which (infinitesimally) small fluctuations acting on a system crossing a critical point decide the system's fate, by determining which branch of a bifurcation is taken. To an outside observe ...
, in which the location of the polarity site is determined randomly. Spontaneous polarization still generates only a single bud site, which has been explained by positive feedback increasing polarity protein concentrations locally at the largest polarity patch while decreasing polarity proteins globally by depleting them. The master regulator of polarity in yeast is
Cdc42, which is a member of the eukaryotic Ras-homologous
Rho-family of GTPases, and a member of the super-family of small GTPases, which include Rop GTPases in plants and small GTPases in prokaryotes. For polarity sites to form, Cdc42 must be present and capable of cycling GTP, a process regulated by its
guanine nucleotide exchange factor
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...
(GEF), Cdc24, and by its
GTPase-activating proteins GTPase-activating proteins or GTPase-accelerating proteins (GAPs) are a family of regulatory proteins whose members can bind to activated G proteins and stimulate their GTPase activity, with the result of terminating the signaling event. GAPs are a ...
(GAPs). Cdc42 localization is further regulated by cell cycle queues, and a number of binding partners. A recent study to elucidate the connection between cell cycle timing and
Cdc42 accumulation in the bud site uses
optogenetics
Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individu ...
to control protein localization using light. During mating, these polarity sites can relocate. Mathematical modeling coupled with imaging experiments suggest the relocation is mediated by actin-driven vesicle delivery.
Vertebrate development
The bodies of vertebrate animals are asymmetric along three axes:
anterior-posterior (head to tail),
dorsal-ventral (spine to belly), and left-right (for example, our heart is on the left side of our body). These polarities arise within the developing embryo through a combination of several processes: 1)
asymmetric cell division
An asymmetric cell division produces two daughter cells with different cellular fates. This is in contrast to symmetric cell divisions which give rise to daughter cells of equivalent fates. Notably, stem cells divide asymmetrically to give rise to ...
, in which two daughter cells receive different amounts of cellular material (e.g. mRNA, proteins), 2) asymmetric localization of specific proteins or RNAs within cells (which is often mediated by the cytoskeleton), 3) concentration gradients of secreted proteins across the embryo such as
Wnt,
Nodal
Nodal homolog is a secretory protein that in humans is encoded by the ''NODAL'' gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta superfamily (TGF-β superfamily). Like many other members of this superf ...
, and
Bone Morphogenic Proteins
Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of piv ...
(BMPs), and 4) differential expression of membrane receptors and ligands that cause lateral inhibition, in which the receptor-expressing cell adopts one fate and its neighbors another.
In addition to defining asymmetric axes in the adult organism, cell polarity also regulates both individual and collective cell movements during embryonic development such as
apical constriction Apical constriction is the process in which contraction of the apical side of a cell causes the cell to take on a wedged shape. Generally, this shape change is coordinated across many cells of an epithelial layer, generating forces that can bend or ...
,
invagination
Invagination is the process of a surface folding in on itself to form a cavity, pouch or tube. In developmental biology, invagination is a mechanism that takes place during gastrulation. This mechanism or cell movement happens mostly in the vegetal ...
, and
epiboly Epiboly describes one of the five major types of cell movements that occur in the gastrulation stage of embryonic development of some organisms. Epiboly is the spreading and thinning of the ectoderm while the endoderm and mesoderm layers move to the ...
. These movements are critical for shaping the embryo and creating the complex structures of the adult body.
Molecular basis
Cell polarity arises primarily through the localization of specific proteins to specific areas of the cell membrane. This localization often requires both the recruitment of cytoplasmic proteins to the cell membrane and polarized
vesicle transport
In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis) and transport of mater ...
along
cytoskeletal
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compo ...
filaments to deliver transmembrane proteins from the
golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
. Many of the molecules responsible for regulating cell polarity are conserved across cell types and throughout metazoan species. Examples include the PAR complex (
Cdc42, PAR3/ASIP, PAR6, atypical
protein kinase C
In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
), Crumbs complex (Crb, PALS, PATJ, Lin7), and Scribble complex (Scrib, Dlg, Lgl). These polarity complexes are localized at the cytoplasmic side of the cell membrane, asymmetrically within cells. For example, in epithelial cells the PAR and Crumbs complexes are localized along the apical membrane and the Scribble complex along the lateral membrane. Together with a group of signaling molecules called
Rho GTPases
Rho GTPase may refer to:
*Any member of the Rho family of GTPases
*The members of the Rho family of GTPases belonging to the '' Rho subclass''
*RHOA
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase p ...
, these polarity complexes can regulate vesicle transport and also control the localization of cytoplasmic proteins primarily by regulating the phosphorylation of phospholipids called
phosphoinositides
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
. Phosphoinositides serve as docking sites for proteins at the cell membrane, and their state of phosphorylation determines which proteins can bind.
Polarity establishment
While many of the key polarity proteins are well conserved, different mechanisms exist to establish cell polarity in different cell types. Here, two main classes can be distinguished: (1) cells that are able to polarize spontaneously, and (2) cells that establish polarity based on intrinsic or environmental cues.
Spontaneous symmetry breaking can be explained by amplification of stochastic fluctuations of molecules due to non-linear chemical kinetics. The mathematical basis for this biological phenomenon was established by
Alan Turing
Alan Mathison Turing (; 23 June 1912 – 7 June 1954) was an English mathematician, computer scientist, logician, cryptanalyst, philosopher, and theoretical biologist. Turing was highly influential in the development of theoretical com ...
in his 1953 paper '
The chemical basis of morphogenesis
"The Chemical Basis of Morphogenesis" is an article that the English mathematician Alan Turing wrote in 1952. It describes how patterns in nature, such as stripes and spirals, can arise naturally from a homogeneous, uniform state. The theory, w ...
.' While Turing initially attempted to explain pattern formation in a multicellular system, similar mechanisms can also be applied to intracellular pattern formation. Briefly, if a network of at least two interacting chemicals (in this case, proteins) exhibits certain types of reaction kinetics, as well as differential diffusion, stochastic concentration fluctuations can give rise to the formation of large-scale stable patterns, thus bridging from a molecular length scale to a cellular or even tissue scale.
A prime example for the second type of polarity establishment, which relies on extracellular or intracellular cues, is the ''C. elegans'' zygote. Here, mutual inhibition between two sets of proteins guides polarity establishment and maintenance. On the one hand, PAR-3, PAR-6 and aPKC (called anterior PAR proteins) occupy both the plasma membrane and cytoplasm prior to symmetry breaking. PAR-1, the ''C. elegans''-specific ring-finger-containing protein PAR-2, and LGL-1 (called posterior PAR proteins) are present mostly in the cytoplasm. The male centrosome provides a cue, which breaks an initially homogenous membrane distribution of anterior PARs by inducing cortical flows. These are thought to advect anterior PARs towards one side of the cell, allowing posterior PARs to bind to other pole (posterior).
Anterior and posterior PAR proteins then maintain polarity until cytokinesis by mutually excluding each other from their respective cell membrane areas.
See also
*
Epithelial polarity Epithelial polarity is one example of the cell polarity that is a fundamental feature of many types of cells. Epithelial cells feature distinct 'apical', 'lateral' and 'basal' plasma membrane domains. Epithelial cells connect to one another via th ...
*
Cell migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ...
*
Embryogenesis
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
*
Embryonic development
An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
*
Asymmetric cell division
An asymmetric cell division produces two daughter cells with different cellular fates. This is in contrast to symmetric cell divisions which give rise to daughter cells of equivalent fates. Notably, stem cells divide asymmetrically to give rise to ...
*
3D cell culture
3-D, 3D, or 3d may refer to:
Science, technology, and mathematics Relating to three-dimensionality
* Three-dimensional space
** 3D computer graphics, computer graphics that use a three-dimensional representation of geometric data
** 3D film, a ...
*
Cell culture assay
*
Madin-Darby canine kidney cells
Madin-Darby canine kidney (MDCK) cells are a model mammalian cell line used in biomedical research. MDCK cells are used for a wide variety of cell biology studies including cell polarity, cell-cell adhesions (termed adherens junctions), collecti ...
References
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Cell biology