Vimentin
Encyclopedia
Vimentin is a type III intermediate filament
(IF) 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
. All IF proteins are expressed in a highly developmentally-regulated fashion; vimentin is the major cytoskeletal component of mesenchymal cells. Because of this, vimentin is often used as a marker of mesenchymally-derived cells or cells undergoing an epithelial-to-mesenchymal transition
(EMT) during both normal development and metastatic progression.
, capped on each end by non-helical amino (head) and carboxyl (tail) domains. Two monomers are likely co-translationally expressed in a way that facilitates their formation of a coiled-coil dimer, which is the basic subunit of vimentin assembly.
The α-helical sequences contain a pattern of hydrophobic amino acids that contribute to forming a "hydrophobic seal" on the surface of the helix. In addition, there is a periodic distribution of acidic and basic amino acids that seems to play an important role in stabilizing coiled-coil dimers. The spacing of the charged residues is optimal for ionic salt bridges
, which allows for the stabilization of the α-helix structure. While this type of stabilization is intuitive for intrachain interactions, rather than interchain interactions, scientists have proposed that perhaps the switch from intrachain salt bridges formed by acidic and basic residues to the interchain ionic associations contributes to the assembly of the filament.
. Vimentin is attached to the nucleus
, endoplasmic reticulum
, and mitochondria, either laterally or terminally.
Vimentin Clips offers three different clips that show vimentin movement inside the cell.
The dynamic nature of vimentin is important when offering flexibility to the cell. Scientists found that vimentin provided cells with a resilience absent from the microtubule or actin filament networks, when under mechanical stress in vivo. Therefore, in general, it is accepted that vimentin is the cytoskeletal component responsible for maintaining cell integrity. (It was found that cells without vimentin are extremely delicate when disturbed with a micropuncture.)
Results of a study involving transgenic mice that lacked vimentin showed that the mice were functionally normal. While the outcome might seem surprising, it is possible that the microtubule network may have compensated for the absence of the intermediate network. This strengthens the suggestion of intimate interactions between microtubules and vimentin. Moreover, when microtubule depolymerizers were present, vimentin reorganization occurred, once again implying a relationship between the two systems.
Vimentin Images offers a gallery of images in which vimentin and other cytoskeletal structures are labeled. These images allow the visualization of interactions between vimentin and other cytoskeletal components.
In essence, vimentin is responsible for maintaining cell shape, integrity of the cytoplasm, and stabilizing cytoskeletal interactions.
Also, vimentin is found to control the transport of low-density lipoprotein, LDL, -derived cholesterol
from a lysosome
to the site of esterification. With the blocking of transport of LDL-derived cholesterol inside the cell, cells were found to store a much lower percentage of the lipoprotein
than normal cells with vimentin. This dependence seems to be the first process of a biochemical function in any cell that depends on a cellular intermediate filament network. This type of dependence has ramifications on the adrenal cells, which rely on cholesteryl esters derived from LDL.
tumor marker
to identify mesenchyme
.
See also Anti-citrullinated protein antibody
for its use in diagnosis of rheumatoid arthritis
.
with UPP1
, MYST2
, Desmoplakin
, Plectin
, SPTAN1
, MEN1
, Protein kinase N1
and YWHAZ
.
The 3' UTR of Vimentin mRNA
has been found to bind a 46kDa protein.
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...
(IF) protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
as well as bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. IF, along with tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
-based microtubules and 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...
-based microfilaments, comprise 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...
. All IF proteins are expressed in a highly developmentally-regulated fashion; vimentin is the major cytoskeletal component of mesenchymal cells. Because of this, vimentin is often used as a marker of mesenchymally-derived cells or cells undergoing an epithelial-to-mesenchymal transition
Epithelial-mesenchymal transition
Epithelial-mesenchymal transition or transformation is a hypothesized program of development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility...
(EMT) during both normal development and metastatic progression.
Structure
A vimentin monomer, like all other intermediate filaments, has a central α-helical domainProtein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
, capped on each end by non-helical amino (head) and carboxyl (tail) domains. Two monomers are likely co-translationally expressed in a way that facilitates their formation of a coiled-coil dimer, which is the basic subunit of vimentin assembly.
The α-helical sequences contain a pattern of hydrophobic amino acids that contribute to forming a "hydrophobic seal" on the surface of the helix. In addition, there is a periodic distribution of acidic and basic amino acids that seems to play an important role in stabilizing coiled-coil dimers. The spacing of the charged residues is optimal for ionic salt bridges
Salt bridge (protein)
Salt bridges fall into the broader category of noncovalent interactions. A salt bridge is actually a combination of two noncovalent interactions: hydrogen bonding and electrostatic interactions . This is most commonly observed to contribute stability to the entropically unfavorable folded...
, which allows for the stabilization of the α-helix structure. While this type of stabilization is intuitive for intrachain interactions, rather than interchain interactions, scientists have proposed that perhaps the switch from intrachain salt bridges formed by acidic and basic residues to the interchain ionic associations contributes to the assembly of the filament.
Function
Vimentin plays a significant role in supporting and anchoring the position of the organelles in the cytosolCytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
. Vimentin is attached to the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
, and mitochondria, either laterally or terminally.
Vimentin Clips offers three different clips that show vimentin movement inside the cell.
The dynamic nature of vimentin is important when offering flexibility to the cell. Scientists found that vimentin provided cells with a resilience absent from the microtubule or actin filament networks, when under mechanical stress in vivo. Therefore, in general, it is accepted that vimentin is the cytoskeletal component responsible for maintaining cell integrity. (It was found that cells without vimentin are extremely delicate when disturbed with a micropuncture.)
Results of a study involving transgenic mice that lacked vimentin showed that the mice were functionally normal. While the outcome might seem surprising, it is possible that the microtubule network may have compensated for the absence of the intermediate network. This strengthens the suggestion of intimate interactions between microtubules and vimentin. Moreover, when microtubule depolymerizers were present, vimentin reorganization occurred, once again implying a relationship between the two systems.
Vimentin Images offers a gallery of images in which vimentin and other cytoskeletal structures are labeled. These images allow the visualization of interactions between vimentin and other cytoskeletal components.
In essence, vimentin is responsible for maintaining cell shape, integrity of the cytoplasm, and stabilizing cytoskeletal interactions.
Also, vimentin is found to control the transport of low-density lipoprotein, LDL, -derived cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
from a lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
to the site of esterification. With the blocking of transport of LDL-derived cholesterol inside the cell, cells were found to store a much lower percentage of the lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
than normal cells with vimentin. This dependence seems to be the first process of a biochemical function in any cell that depends on a cellular intermediate filament network. This type of dependence has ramifications on the adrenal cells, which rely on cholesteryl esters derived from LDL.
Clinical significance
It has been used as a sarcomaSarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...
tumor marker
Tumor marker
A tumor marker is a substance found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer...
to identify mesenchyme
Mesenchyme
Mesenchyme, or mesenchymal connective tissue, is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm, although some are derived from other germ layers; e.g. some mesenchyme is derived from neural crest cells and thus originates from the ectoderm...
.
See also Anti-citrullinated protein antibody
Anti-citrullinated protein antibody
Anti-citrullinated protein antibodies or anti-cyclic citrullinated protein antibodies are autoantibodies that are frequently detected in the blood of rheumatoid arthritis patients...
for its use in diagnosis of rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
.
Interactions
Vimentin 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 UPP1
UPP1
Uridine phosphorylase 1 is an enzyme that in humans is encoded by the UPP1 gene.-Further reading:...
, MYST2
MYST2
Histone acetyltransferase MYST2 is an enzyme that in humans is encoded by the MYST2 gene.-Interactions:MYST2 has been shown to interact with Androgen receptor, ORC1L and Vimentin.-Further reading:...
, 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...
, Plectin
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...
, 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...
, MEN1
MEN1
Menin is a protein that in humans is encoded by the MEN1 gene. Menin is a putative tumor suppressor associated with multiple endocrine neoplasia type 1....
, Protein kinase N1
Protein kinase N1
Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene.-Interactions:Protein kinase N1 has been shown to interact with Phospholipase D1, Phosphoinositide-dependent kinase-1, Vimentin, AKAP9, CCDC85B, Actinin, alpha 1, NEFL, NEUROD2 and RHOA.-Further reading:...
and YWHAZ
YWHAZ
14-3-3 protein zeta/delta is a protein that in humans is encoded by the YWHAZ gene.-Interactions:YWHAZ has been shown to interact with TSC2, LIMK1, CDC25B, AKT1, BCAR1, Interleukin-9 receptor, C-Raf, HMGN1, Vimentin, Tau protein, Protein kinase Mζ, GP1BB, GP1BA, TNFAIP3, Bcl-2-associated death...
.
The 3' UTR of Vimentin mRNA
Vimentin 3' UTR protein-binding region
The vimentin 3' UTR protein-binding region is an RNA element that contains a Y shaped structure which has been shown to have protein binding activity. The same region has been implicated in the control of mRNA localisation to the perinuclear region of the cytoplasm, possibly at sites of...
has been found to bind a 46kDa protein.