Vimentin
Template:Short description Template:Cs1 config Template:Infobox gene
Vimentin is a structural protein that in humans is encoded by the VIM gene. Its name comes from the Latin vimentum which refers to an array of flexible rods.<ref name="pmid368806">Template:Cite journal</ref>
Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal cells. IF proteins are found in all animal cells<ref name="Eriksson">Template:Cite journal</ref> as well as bacteria.<ref name="Cabeen">Template:Cite journal</ref> Intermediate filaments, 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.
Structure
The assembly of the fibrous vimentin filament that forms the cytoskeleton follows a gradual sequence. The vimentin monomer has a central α-helical domain, capped on each end by non-helical amino (head) and carboxyl (tail) domains.<ref name="fuchs">Template:Cite journal</ref> Two monomers are likely co-translationally expressed in a way that facilitates their interaction forming a coiled-coil dimer, which is the basic subunit of vimentin assembly.<ref name="chang">Template:Cite journal</ref> A pair of coiled-coil dimers connect in an antiparallel fashion to form a tetramer. Eight tetramers join to form what is known as the unit-length filament (ULF), ULFs then stick to each other and elongate followed by compaction to form the fibrous proteins.<ref>Template:Cite journal</ref>
The α-helical sequences contain a pattern of hydrophobic amino acids that contribute to forming a "hydrophobic seal" on the surface of the helix.<ref name="fuchs" /> 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.<ref name="fuchs" /> 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.<ref name="fuchs" />
Function
Vimentin plays a significant role in supporting and anchoring the position of the organelles in the cytosol. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally.<ref name="katsumoto">Template:Cite journal</ref>
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).<ref name="goldman">Template:Cite journal</ref> Transgenic mice that lack vimentin appeared normal and did not show functional differences.<ref name="Golucci-Guyon">Template:Cite journal</ref> It is possible that the microtubule network may have compensated for the absence of the intermediate network. This result supports an intimate interaction between microtubules and vimentin. Moreover, when microtubule depolymerizers were present, vimentin reorganization occurred, once again implying a relationship between the two systems.<ref name="goldman" /> On the other hand, wounded mice that lack the vimentin gene heal slower than their wild type counterparts.<ref name="Eckes2000">Template:Cite journal</ref>
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 JUNQ and IPOD inclusion bodies in asymmetric division of mammalian cell lines.<ref name="pmid24843142">Template:Cite journal</ref>
Also, vimentin is found to control the transport of low-density lipoprotein, LDL, -derived cholesterol from a lysosome to the site of esterification.<ref name="sarria">Template:Cite journal</ref> 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.<ref name="sarria" />
Vimentin plays a role in aggresome formation, where it forms a cage surrounding a core of aggregated protein.<ref name="pmid9864362">Template:Cite journal</ref>
In addition to its conventional intracellular localisation, vimentin can be found extracellularly. Vimentin can be expressed as a cell surface protein and have suggested roles in immune reactions. It can also be released in phosphorylated forms to the extracellular space by activated macrophages, astrocytes are also known to release vimentin.<ref>Template:Cite journal</ref>
Clinical significance
It has been used as a sarcoma tumor marker to identify mesenchyme, though its specificity as a bio marker has been disputed.<ref name="pmid2435649">Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}Template:Cbignore</ref> Vimentin is present in spindle cell squameous cell carcinoma.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
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.<ref name="pmid22315367">Template:Cite journal</ref> High levels of DNA methylation in the promoter region have also been associated with markedly decreased survival in hormone positive breast cancers.<ref>Template:Cite journal</ref> Downregulation of vimentin was identified in cystic variant of papillary thyroid carcinoma using a proteomic approach.<ref name="pmid25978681">Template:Cite journal</ref> See also Anti-citrullinated protein antibody for its use in diagnosis of rheumatoid arthritis. Vimentin has also been found to be an attachment factor for SARS-CoV-2.<ref>Template:Cite journal</ref>
Interactions
Vimentin has been shown to interact with:
- DSP<ref name = pmid9261168>Template:Cite journal</ref>
- MEN1<ref name = pmid12169273>Template:Cite journal</ref>
- MYST2<ref name = pmid16189514>Template:Cite journal</ref><ref name = pmid16169070>Template:Cite journal</ref>
- PKN1<ref name = pmid9175763>Template:Cite journal</ref>
- PRKCI<ref name="pmid29048609">Template:Cite journal</ref><ref name="pmid29781749">Template:Cite journal</ref>
- PLEC<ref name = pmid3027087>Template:Cite journal</ref><ref name = pmid11441066>Template:Cite journal</ref>
- SPTAN1<ref name = pmid11441066/>
- UPP1<ref name = pmid11278417>Template:Cite journal</ref>
- YWHAZ<ref name = pmid10887173>Template:Cite journal</ref>
The 3' UTR of Vimentin mRNA has been found to bind a 46kDa protein.<ref name="pmid9241253">Template:Cite journal</ref>
References
Further reading
External links
Template:PDB Gallery Template:Cytoskeletal Proteins Template:Tumor markers