Plectin
Encyclopedia
Plectin is a giant protein
(c500 kDa) found in nearly all mammalian cells
which acts as a link between the three main components of the cytoskeleton
: actin
microfilaments, microtubule
s and intermediate filament
s. 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
.
consisting of a central coiled coil
of alpha helices connected to large globular domains 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 six of this domain is known to connect to the intermediate filaments cytokeratin
and vimentin
. At the opposite end of the protein, in the N-terminal domain, a region has been defined as responsible for binding to actin
. In 2004 the exact crystal structure of this actin
binding domain(ABD) was determined in mice and shown to be composed of two calponin
homology(CH) domains.
experiments plectin has been found to associate with all three major components of the cytoskeleton. With the use of microscopy especially plectin has been shown to directly connect microtubules to intermediate filaments as well as to each other. While plectin has been observed to mediate interactions between actin and intermediate filaments and associate with each independently, a direct linkage by plectin between these two filaments has not been completely proven. It may be that plectin actually connects to proteins associated with each rather than directly.
Besides serving as a linker protein between the main elements of the cytoskeleton, plectin also forms connections between other cytoskeletally related proteins as well. Plectin has been shown to directly link Myosin
II motor proteins and intermediate filaments. In in vitro assays plectin has been found to bind subplasma membrane skeleton proteins such as alpha-spectrin and fodrin.
Over the past decade plectin has been identified as an important component linking the cytoskeleton to intercellular junctions which enable the structural integrity of a tissue as a whole. Two such junctions, Desmosomes and Hemidesmosomes which link intermediate filament networks between cells have been shown to associate with plectin. Plectin has been revealed to localize to the desmosomes and in vitro studies have shown that it can form bridges between the desmosome protein, desmoplakin
and intermediate filaments. In hemidesmosomes plectin has been shown to interact with the integrin
β4 subunits of the hemidesmosome plaque and function in a clamp like manner to crosslink the intermediate filament, cytokeratin
to the junction.
with SPTAN1
and Vimentin
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
(c500 kDa) found in nearly all mammalian cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
which acts as a link between the three main components of the cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
: actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
microfilaments, microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s and intermediate filament
Intermediate filament
Intermediate filaments are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin , and that of 25 nm microtubules, although they were initially designated...
s. 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
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
.
Structure
The structure of plectin is thought to be a dimerProtein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
consisting of a central coiled coil
Coiled coil
A coiled coil is a structural motif in proteins, in which 2-7 alpha-helices are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g. transcription factors...
of alpha helices connected to large globular domains 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 six of this domain is known to connect to the intermediate filaments cytokeratin
Cytokeratin
Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s when the protein subunits of keratin intermediate filaments inside cells were first being identified and...
and vimentin
Vimentin
Vimentin is a type III intermediate filament protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprise the cytoskeleton...
. At the opposite end of the protein, in the N-terminal domain, a region has been defined as responsible for binding to actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
. In 2004 the exact crystal structure of this actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
binding domain(ABD) was determined in mice and shown to be composed of two calponin
Calponin
Calponin is a calcium binding protein. Calponin tonically inhibits the ATPase activity of myosin in smooth muscle. Phosphorylation of calponin by a protein kinase, which is dependent upon calcium binding to calmodulin, releases the calponin's inhibition of the smooth muscle ATPase.- Sturcture and...
homology(CH) domains.
Function
Through the use of gold-immunoelectron microscopy, immunoblotting and immunofluorescenceImmunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
experiments plectin has been found to associate with all three major components of the cytoskeleton. With the use of microscopy especially plectin has been shown to directly connect microtubules to intermediate filaments as well as to each other. While plectin has been observed to mediate interactions between actin and intermediate filaments and associate with each independently, a direct linkage by plectin between these two filaments has not been completely proven. It may be that plectin actually connects to proteins associated with each rather than directly.
Besides serving as a linker protein between the main elements of the cytoskeleton, plectin also forms connections between other cytoskeletally related proteins as well. Plectin has been shown to directly link Myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
II motor proteins and intermediate filaments. In in vitro assays plectin has been found to bind subplasma membrane skeleton proteins such as alpha-spectrin and fodrin.
Over the past decade plectin has been identified as an important component linking the cytoskeleton to intercellular junctions which enable the structural integrity of a tissue as a whole. Two such junctions, Desmosomes and Hemidesmosomes which link intermediate filament networks between cells have been shown to associate with plectin. Plectin has been revealed to localize to the desmosomes and in vitro studies have shown that it can form bridges between the desmosome protein, desmoplakin
Desmoplakin
Desmoplakin is a protein associated with desmosomes.Desmoplakin is a protein that in humans is encoded by the DSP gene. The C-terminus of desmoplakin binds with intermediate filaments. These are further sub divided to three homologous Plakin repeat domains . In the mid-region of desmoplakin, a...
and intermediate filaments. In hemidesmosomes plectin has been shown to interact with the integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
β4 subunits of the hemidesmosome plaque and function in a clamp like manner to crosslink the intermediate filament, cytokeratin
Cytokeratin
Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s when the protein subunits of keratin intermediate filaments inside cells were first being identified and...
to the junction.
Interactions
Plectin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with SPTAN1
SPTAN1
Spectrin alpha chain, brain is a protein that in humans is encoded by the SPTAN1 gene.The spectrins are a family of widely-distributed cytoskeletal proteins which are involved in actin crosslinking. The protein enocoded by this gene is a spectrin alpha-chain which heterodimerizes with...
and Vimentin
Vimentin
Vimentin is a type III intermediate filament protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprise the cytoskeleton...
.