Vimentin Explained

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.[1]

Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal cells. IF proteins are found in all animal cells[2] as well as bacteria.[3] Intermediate filaments, along with tubulin-based microtubules and actin-based microfilaments, comprises 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.[4] 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.[5] 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. [6]

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.

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.[7]

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).[8] Transgenic mice that lack vimentin appeared normal and did not show functional differences.[9] 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. On the other hand, wounded mice that lack the vimentin gene heal slower than their wild type counterparts.[10]

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.[11]

Also, vimentin is found to control the transport of low-density lipoprotein, LDL, -derived cholesterol from a lysosome to the site of esterification.[12] 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.

Vimentin plays a role in aggresome formation, where it forms a cage surrounding a core of aggregated protein.[13]

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. [14]

Clinical significance

It has been used as a sarcoma tumor marker to identify mesenchyme.[15] [16] Its specificity as a biomarker has been disputed by Jerad Gardner.[17] Vimentin is present in spindle cell squameous cell carcinoma.[18] [19]

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.[20] High levels of DNA methylation in the promoter region have also been associated with markedly decreased survival in hormone positive breast cancers.[21] Downregulation of vimentin was identified in cystic variant of papillary thyroid carcinoma using a proteomic approach.[22] See also Anti-citrullinated protein antibody for its use in diagnosis of rheumatoid arthritis.

Vimentin was discovered to be an attachment factor for SARS-CoV-2 by Nader Rahimi and colleagues.[23]

Interactions

Vimentin has been shown to interact with:

The 3' UTR of Vimentin mRNA has been found to bind a 46kDa protein.[35]

Further reading

External links

Notes and References

  1. Franke WW, Schmid E, Osborn M, Weber K . Different intermediate-sized filaments distinguished by immunofluorescence microscopy . Proceedings of the National Academy of Sciences of the United States of America . 75 . 10 . 5034–5038 . October 1978 . 368806 . 336257 . 10.1073/pnas.75.10.5034 . free . 1978PNAS...75.5034F .
  2. Eriksson JE, Dechat T, Grin B, Helfand B, Mendez M, Pallari HM, Goldman RD . Introducing intermediate filaments: from discovery to disease . The Journal of Clinical Investigation . 119 . 7 . 1763–1771 . July 2009 . 19587451 . 2701876 . 10.1172/JCI38339 .
  3. Cabeen MT, Jacobs-Wagner C . The bacterial cytoskeleton . Annual Review of Genetics . 44 . 365–392 . 2010 . 21047262 . 10.1146/annurev-genet-102108-134845 .
  4. Fuchs E, Weber K . Intermediate filaments: structure, dynamics, function, and disease . Annual Review of Biochemistry . 63 . 345–382 . 1994 . 7979242 . 10.1146/annurev.bi.63.070194.002021 .
  5. Chang L, Shav-Tal Y, Trcek T, Singer RH, Goldman RD . Assembling an intermediate filament network by dynamic cotranslation . The Journal of Cell Biology . 172 . 5 . 747–758 . February 2006 . 16505169 . 2063706 . 10.1083/jcb.200511033 .
  6. Danielsson F, Peterson MK, Caldeira Araújo H, Lautenschläger F, Gad AK . Vimentin Diversity in Health and Disease . Cells . 7 . 10 . 147 . September 2018 . 30248895 . 6210396 . 10.3390/cells7100147 . free .
  7. Katsumoto T, Mitsushima A, Kurimura T . The role of the vimentin intermediate filaments in rat 3Y1 cells elucidated by immunoelectron microscopy and computer-graphic reconstruction . Biology of the Cell . 68 . 2 . 139–146 . 1990 . 2192768 . 10.1016/0248-4900(90)90299-I . 29019928 .
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  9. Colucci-Guyon E, Portier MM, Dunia I, Paulin D, Pournin S, Babinet C . Mice lacking vimentin develop and reproduce without an obvious phenotype . Cell . 79 . 4 . 679–694 . November 1994 . 7954832 . 10.1016/0092-8674(94)90553-3 . 28146121 .
  10. Eckes B, Colucci-Guyon E, Smola H, Nodder S, Babinet C, Krieg T, Martin P . Impaired wound healing in embryonic and adult mice lacking vimentin . Journal of Cell Science . 113 . 13 . 2455–2462 . July 2000 . 10852824 . 10.1242/jcs.113.13.2455 .
  11. Ogrodnik M, Salmonowicz H, Brown R, Turkowska J, Średniawa W, Pattabiraman S, Amen T, Abraham AC, Eichler N, Lyakhovetsky R, Kaganovich D . 6 . Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin . Proceedings of the National Academy of Sciences of the United States of America . 111 . 22 . 8049–8054 . June 2014 . 24843142 . 4050583 . 10.1073/pnas.1324035111 . free . 2014PNAS..111.8049O .
  12. Sarria AJ, Panini SR, Evans RM . A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells . The Journal of Biological Chemistry . 267 . 27 . 19455–19463 . September 1992 . 1527066 . 10.1016/S0021-9258(18)41797-8 . free .
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  14. Paulin D, Lilienbaum A, Kardjian S, Agbulut O, Li Z . Vimentin: Regulation and pathogenesis . Biochimie . 197 . 96–112 . June 2022 . 35151830 . 10.1016/j.biochi.2022.02.003 . 246778685 . free .
  15. Leader M, Collins M, Patel J, Henry K . Vimentin: an evaluation of its role as a tumour marker . Histopathology . 11 . 1 . 63–72 . January 1987 . 2435649 . 10.1111/j.1365-2559.1987.tb02609.x . 34804720 .
  16. Web site: Immunohistochemistry from the Washington Animal Disease Diagnostic laboratory (WADDL)of the College of Veterinary Medicine, Washington State University. 2009-03-14. https://web.archive.org/web/20081201043331/http://www.vetmed.wsu.edu/depts_waddl/ICS.aspx. 2008-12-01. dead.
  17. Web site: Gardner J . 23 September 2010. How to Interpret Vimentin Immunostain. https://ghostarchive.org/varchive/youtube/20211212/UDnp14nnNC4. 2021-12-12. live. YouTube.
  18. P63 is a useful marker for cutaneous spindle cell squamous cell carcinoma . 16776716 . 2006 . Dotto . J. E. . Glusac . E. J. . Journal of Cutaneous Pathology . 33 . 6 . 413–417 . 10.1111/j.0303-6987.2006.00477.x . 38273016 .
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  20. Moinova H, Leidner RS, Ravi L, Lutterbaugh J, Barnholtz-Sloan JS, Chen Y, Chak A, Markowitz SD, Willis JE . 6 . Aberrant vimentin methylation is characteristic of upper gastrointestinal pathologies . Cancer Epidemiology, Biomarkers & Prevention . 21 . 4 . 594–600 . April 2012 . 22315367 . 3454489 . 10.1158/1055-9965.EPI-11-1060 .
  21. Ulirsch J, Fan C, Knafl G, Wu MJ, Coleman B, Perou CM, Swift-Scanlan T . Vimentin DNA methylation predicts survival in breast cancer . Breast Cancer Research and Treatment . 137 . 2 . 383–396 . January 2013 . 23239149 . 3838916 . 10.1007/s10549-012-2353-5 .
  22. Dinets A, Pernemalm M, Kjellin H, Sviatoha V, Sofiadis A, Juhlin CC, Zedenius J, Larsson C, Lehtiö J, Höög A . 6 . Differential protein expression profiles of cyst fluid from papillary thyroid carcinoma and benign thyroid lesions . PLOS ONE . 10 . 5 . e0126472 . 2015 . 25978681 . 4433121 . 10.1371/journal.pone.0126472 . free . 2015PLoSO..1026472D .
  23. Amraei R, Xia C, Olejnik J, White MR, Napoleon MA, Lotfollahzadeh S, Hauser BM, Schmidt AG, Chitalia V, Mühlberger E, Costello CE, Rahimi N . 6 . Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells . Proceedings of the National Academy of Sciences of the United States of America . 119 . 6 . February 2022 . 35078919 . 8833221 . 10.1073/pnas.2113874119 . free . 2022PNAS..11913874A . e2113874119 .
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