Vimentin

Vimentin is a is_associated_with::protein that in humans is encoded by the VIM is_associated_with::gene.

Vimentin is a type III is_associated_with::intermediate filament (IF) protein that is expressed in is_associated_with::mesenchymal cells. IF proteins are found in all metazoan cells as well as is_associated_with::bacteria. IF, along with is_associated_with::tubulin-based is_associated_with::microtubules and is_associated_with::actin-based microfilaments, comprise the is_associated_with::cytoskeleton. All IF proteins are expressed in a highly developmentally-regulated fashion; vimentin is the major cytoskeletal component of is_associated_with::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.

Structure
A vimentin monomer, like all other intermediate filaments, has a central α-helical domain, capped on each end by non-is_associated_with::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 is_associated_with::amino acids that seems to play an important role in stabilizing is_associated_with::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.

Function
Vimentin plays a significant role in supporting and anchoring the position of the organelles in the is_associated_with::cytosol. Vimentin is attached to the nucleus, is_associated_with::endoplasmic reticulum, and is_associated_with::mitochondria, either laterally or terminally.

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). is_associated_with::Transgenic mice that lack vimentin appeared normal and did not show functional differences. It is possible that the microtubule network may have compensated for the absence of the intermediate network. This result supports an intimate interactions between microtubules and vimentin. Moreover, when microtubule depolymerizers were present, vimentin reorganization occurred, once again implying a relationship between the two systems. On the other hand, wounded mice that lack the vimentin gene heal slower than their wild type counterparts.

In essence, vimentin is responsible for maintaining cell shape, integrity of the cytoplasm, and stabilizing cytoskeletal interactions. Vimentin has been shown to eliminate toxic proteins in is_associated_with::JUNQ and IPOD is_associated_with::inclusion bodies in asymmetric division of mammalian cell lines.

Also, vimentin is found to control the transport of is_associated_with::low-density lipoprotein, LDL, -derived is_associated_with::cholesterol from a is_associated_with::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 is_associated_with::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.

Clinical significance
It has been used as a is_associated_with::sarcoma is_associated_with::tumor marker to identify is_associated_with::mesenchyme.

Methylation of the vimentin gene has been established as a biomarker of colon cancer and this is being utilized in the development of fecal tests for colon cancer. Statistically significant levels of vimentin gene methylation have also been observed in certain upper gastrointestinal pathologies such as Barrett's esophagus, esophageal adenocarcinoma, and intestinal type gastric cancer. High levels of DNA methylation in the promotor region have also been associated with markedly decreased survival in hormone positive breast cancers.

See also is_associated_with::Anti-citrullinated protein antibody for its use in diagnosis of is_associated_with::rheumatoid arthritis.

Interactions
Vimentin has been shown to interact with:


 * DSP
 * is_associated_with::MEN1
 * is_associated_with::MYST2
 * PLEC
 * PKN1
 * is_associated_with::SPTAN1
 * is_associated_with::UPP1
 * is_associated_with::YWHAZ

The 3' UTR of Vimentin mRNA has been found to bind a 46kDa protein.