Nesprin
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Nesprin
Nesprins (nuclear envelope spectrin repeat proteins) are a family of proteins that are found primarily in the outer nuclear membrane, as well as other subcellular compartments. They contain a C-terminal KASH transmembrane domain and are part of the LINC complex (Linker of Nucleoskeleton and Cytoskeleton) which is a protein network that associates the nuclear envelope (the membrane surrounding the nucleus) to the cytoskeleton, outside the nucleus, and the nuclear lamina, inside the nucleus. Nesprin-1 and -2 bind to the actin filaments. Nesprin-3 binds to plectin, which is bound to the intermediate filaments Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''. Intermedia ..., while nesprin-4 interacts with kinesin-1. Nesprin mediated connections to the cytoskeleton provides mechanosensory functions i ...
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Nuclear Envelope
The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membranes: an inner nuclear membrane and an outer nuclear membrane. The space between the membranes is called the perinuclear space. It is usually about 10–50 nm wide. The outer nuclear membrane is continuous with the endoplasmic reticulum membrane. The nuclear envelope has many nuclear pores that allow materials to move between the cytosol and the nucleus. Intermediate filament proteins called lamins form a structure called the nuclear lamina on the inner aspect of the inner nuclear membrane and give structural support to the nucleus. Structure The nuclear envelope is made up of two lipid bilayer membranes, an inner nuclear membrane and an outer nuclear membrane. These membranes are connected to each other by nuclear pores. Two sets of in ...
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SYNE2
Nesprin-2 is a protein that in humans is encoded by the ''SYNE2'' gene. The human SYNE2 gene consists of 116 exons and encodes nesprin-2, a member of the nuclear envelope (NE) spectrin-repeat (nesprin) family. Nesprins are modular proteins with a central extended spectrin-repeat (SR) rod domain and a C-terminal Klarsicht/ANC-1/Syne homology (KASH) transmembrane domain, which acts as a NE-targeting motif. Nesprin-2 (Nesp2) binds to cytoplasmic F-actin, tethering the nucleus to the cytoskeleton 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 compos ... and maintaining the structural integrity of the nucleus. The human SYNE2 gene encodes a protein of 6,885 amino acids (isoform 1, Nesp2 giant); alternative mRNA splicing produces transcripts encoding a larger isoform and numerous smaller isoforms ...
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KASH Domains
KASH domains are conserved C-terminal protein regions less than ~30 amino acids. KASH is an acronym for Klarsicht, ANC-1, Syne Homology. KASH domains always follow a transmembrane domain. Most proteins containing KASH domains are thought to be involved in the positioning of the nucleus in the cell. KASH domains interact with proteins containing SUN domains in the space between the outer and inner nuclear membranes to bridge the nuclear envelope, and may transfer force from the nucleoskeleton to the cytoplasmic cytoskeleton and enable mechanosensory roles in cells. KASH proteins are thought to largely localize to the outer nuclear membrane, although there are reports of inner nuclear membrane localization of some KASH protein isoforms. Examples of KASH proteins ''Caenorhabditis elegans'' *UNC-83 *ANC-1 *ZYG-12 Mammals *Nesprins-1, 2, 3 and 4 (also called Synes, Mynes, Nuance, Enaptin) ''Drosophila melanogaster'' *Klarsicht *MSP-300 References External links * {{PROSITE, ...
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SYNE1
Enaptin also known as nesprin-1 or synaptic nuclear envelope protein 1 (syne-1) is an actin-binding protein that in humans that is encoded by the SYNE1 gene. Function This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Enaptin is a nuclear envelope protein found in human myocytes and synapses, which is made up of 8,797 amino acids. Enaptin is involved in the maintenance of nuclear organization and structural integrity, tethering the cell nucleus to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. Structure Enaptin contains a coiled alpha-helical region and a large beta-sheet region in the upper part and at least four alpha-helices spliced together, indicating the similarity with collagen. The protein is made up of three main parts, as can be seen in the diagram: cytoplasmic (1-8746), anchor for type IV membrane pr ...
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Spectrin Repeat
Spectrin repeats are found in several proteins involved in cytoskeletal structure. These include spectrin, alpha-actinin, dystrophin and more recently the plakin family. The spectrin repeat forms a three-helix bundle. These conform to the rules of the heptad repeat. Spectrin repeats give rise to linear proteins. This however may be due to sample bias in which linear and rigid structures are more amenable to crystallization. There are hints however, that some proteins harbouring spectrin repeats may also be flexible. This is most likely due to specifically evolved functional purposes. Human proteins containing this domain ACTN1; ACTN2; ACTN3; ACTN4; AKAP6; SYNE3; CATX-15; DMD; DRP2; DST; KALRN; MACF1; MCF2L; SPTA1; SPTAN1; SPTB; SPTBN1; SPTBN2; SPTBN4; SPTBN5; SYNE1; SYNE2; TRIO; UTRN Utrophin is a protein that in humans is encoded by the ''UTRN'' gene. The protein encoded by this gene is a compo ...
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LINC Complex
The LINC complex (Linker of Nucleoskeleton and Cytoskeleton) is a protein complex associated with both inner and outer membranes of the nucleus. It is composed of SUN-domain proteins and KASH-domain proteins. The SUN-domain proteins are associated with both nuclear lamins and chromatin and cross the inner nuclear membrane. They interact with the KASH domain KASH domains are conserved C-terminal protein regions less than ~30 amino acids. KASH is an acronym for Klarsicht, ANC-1, Syne Homology. KASH domains always follow a transmembrane domain. Most proteins containing KASH domains are thought to be in ... proteins in the perinuclear (lumen) space between the two membranes. The KASH domain proteins cross the outer nuclear membrane and interact with actin filaments, microtubule filaments (through dynein and kinesin motors), intermediate filaments (through spectrin), centrosomes and cytoplasmic organelles. The number of SUN-domain and KASH-domain proteins increased in evolution. Func ...
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Actin Filaments
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 proteins in the cell. Microfilaments are usually about 7 nm in diameter and made up of two strands of actin. Microfilament functions include cytokinesis, amoeboid movement, cell motility, changes in cell shape, endocytosis and exocytosis, cell contractility, and mechanical stability. Microfilaments are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton tensile forces. In inducing cell motility, one end of the actin filament elongates while the other end contracts, presumably by myosin II molecular motors. Additionally, they function as part of actomyosin-driven contractile molecular motors, wherein the thin filaments serve as tensile platforms for myosin's ATP-dep ...
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Plectin
Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments. In addition, plectin links the cytoskeleton to junctions found in the plasma membrane that structurally connect different cells. By holding these different networks together, plectin plays an important role in maintaining the mechanical integrity and viscoelastic properties of tissues. Structure Plectin can exist in cells as several alternatively-spliced isoforms, all around 500 kDa and >4000 amino acids. The structure of plectin is thought to be a dimer consisting of a central coiled coil of alpha helices connecting two large globular domains (one at each terminus). These globular domains are responsible for connecting plectin to its various cytoskeletal targets. The carboxy-terminal domain is made of 6 highly homologous repeating regions. The subdomain between regions five and ...
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Intermediate Filaments
Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''. Intermediate filaments are composed of a family of related proteins sharing common structural and sequence features. Initially designated 'intermediate' because their average diameter (10  nm) is between those of narrower microfilaments (actin) and wider myosin filaments found in muscle cells, the diameter of intermediate filaments is now commonly compared to actin microfilaments (7 nm) and microtubules (25 nm). Animal intermediate filaments are subcategorized into six types based on similarities in amino acid sequence and protein structure. Most types are cytoplasmic, but one type, Type V is a nuclear lamin. Unlike microtubules, IF distribution in cells show no good correlation with the distribution of either mitochondria or endopla ...
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Kinesin
A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP) (thus kinesins are ATPases, a type of enzyme). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular cargo, such as in axonal transport, and intraflagellar transport. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo such as protein and membrane components from the center of the cell towards the periphery. This form of transport is known as anterograde transport. In contrast, dyneins are motor proteins that move toward the minus end of a microtubule in retrograde transport. Discovery Kinesins were discovered in 1985, based on their motility in cytoplasm extruded from the giant axon of the squid. They turned out as MT-based anterograde intracellular trans ...
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