Vimentin

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Vimentin
Protein VIM PDB 1gk4.png
PDB rendering based on 1gk4.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols VIM ; CTRCT30; HEL113
External IDs OMIM193060 MGI98932 HomoloGene2538 GeneCards: VIM Gene
RNA expression pattern
PBB GE VIM 201426 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7431 22352
Ensembl ENSG00000026025 ENSMUSG00000026728
UniProt P08670 P20152
RefSeq (mRNA) NM_003380 NM_011701
RefSeq (protein) NP_003371 NP_035831
Location (UCSC) Chr 10:
17.23 – 17.24 Mb
Chr 2:
13.57 – 13.58 Mb
PubMed search [1] [2]
Immunofluorescence staining pattern of vimentin antibodies. Produced by incubating vimentin primary antibodies and FITC labelled secondary antibodies with HEp-20-10 cells.

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

Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells[1] as well as bacteria.[2] 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.

Structure

A vimentin monomer, like all other intermediate filaments, has a central α-helical domain, capped on each end by non-helical amino (head) and carboxyl (tail) domains.[3] 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.[4]

The α-helical sequences contain a pattern of hydrophobic amino acids that contribute to forming a "hydrophobic seal" on the surface of the helix.[3] 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.[3] 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.[3]

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.[5]

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).[6] Transgenic mice that lack vimentin appeared normal and did not show functional differences.[7] 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.[6] On the other hand, wounded mice that lack the vimentin gene heal slower than their wild type counterparts. [8]

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.[9]

Also, vimentin is found to control the transport of low-density lipoprotein, LDL, -derived cholesterol from a lysosome to the site of esterification.[10] 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.[10]

Clinical significance

It has been used as a sarcoma tumor marker to identify mesenchyme.[11][12]

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.[13] High levels of DNA methylation in the promotor region have also been associated with markedly decreased survival in hormone positive breast cancers.[14]

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

Interactions

Vimentin has been shown to interact with:

The 3' UTR of Vimentin mRNA has been found to bind a 46kDa protein.[24]

References

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  8. Eckes B, Colucci-Guyon E, Smola H, Nodder S, Babinet C, Krieg T, Martin P (2000). "Impaired wound healing in embryonic and adult mice lacking vimentin". Journal of cell science. 113: 2455--62. PMID 10852824. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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  10. 10.0 10.1 Sarria AJ, Panini SR, Evans RM (September 1992). "A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells". J. Biol. Chem. 267 (27): 19455–63. PMID 1527066. <templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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  12. "Immunohistochemistry from the Washington Animal Disease Diagnostic laboratory (WADDL)of the College of Veterinary Medicine, Washington State University". Retrieved 2009-03-14.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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  19. Herrmann H, Wiche G (1987). "Plectin and IFAP-300K are homologous proteins binding to microtubule-associated proteins 1 and 2 and to the 240-kilodalton subunit of spectrin". J. Biol. Chem. 262 (3): 1320–5. PMID 3027087.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
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Further reading

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External links