Disease relevance of Vim

• These cerebellar xenografts displayed histologic features and immunohistochemical profiles (microtubule-associated protein 2, glial fibrillary acidic protein, and vimentin) similar to human medulloblastomas [1].
• Four renal cell lines were derived from glomeruli, proximal, distal, and cortical collecting tubules microdissected from the kidneys of transgenic mice carrying the temperature-sensitive mutant of the simian virus 40 large T antigen under the control of the vimentin promoter [2].
• Death in Vim-/- mice resulted from end-stage renal failure [3].
• Here, we used vimentin knockout mice (Vim(-/-)) and an experimental model of acute renal injury (30-min bilateral renal ischemia) to explore the role of vimentin [4].
• To investigate the regulatory mechanisms controlling expression of the vimentin-encoding gene (Vim) during mouse myeloid leukemia M1 cell differentiation, mouse Vim was cloned and the transcriptional activity of its 5' promoter region was analysed by chloramphenicol acetyltransferase (CAT) assay [5].
• We demonstrate here for the first time that the expression of mutated vimentin induces a protein-stress response that contributes to disease pathology in mice, and hypothesise that vimentin mutations cause cataracts in humans [6].

Psychiatry related information on Vim

• Neurofibrillary tangles in senile dementia of the Alzheimer type share an antigenic determinant with intermediate filaments of the vimentin class [7].

High impact information on Vim

• While these results leave open the question of the possible role of vimentin in unusual situations or pathological conditions, they show that a conspicuous developmental and cell-specific structure that is an integral part of the cytoskeleton can be eliminated without apparent effect on mouse reproduction and development [8].
• Mice lacking vimentin develop and reproduce without an obvious phenotype [8].
• To address the biological role of vimentin in the context of the living organism, we have introduced a null mutation of the vimentin gene into the germ line of mice [8].
• Localization of newly synthesized vimentin subunits reveals a novel mechanism of intermediate filament assembly [9].
• During adipose conversion of murine 3T3-L1 cells, the arrangement of vimentin intermediate filaments (IFs) changes from an extended fibrillar state to a complex cage formation tightly associated with the forming lipid globules [10].

Chemical compound and disease context of Vim

• In addition, we also studied the influence of melatonin on the expression of two cell surface adhesion molecules (E-cadherin and beta1 integrin) and an intermediate filament protein (vimentin), the expression of which has been correlated with the relative invasive capacity of human breast cancer cells [11].
• Analysis of 12(S)-HETE effects on B16a melanoma cell cytoskeleton revealed reversible rearrangement of microtubules, microfilaments, the actin-binding proteins, vinculin, myosin heavy (MHC) and light chains (MLC), as well as bundling of vimentin intermediate filaments [12].
• We show that vimentin filaments are present in undifferentiated Friend murine erythroleukemia cells, but are lost progressively to undetectable levels by 96 h of dimethyl sulfoxide-mediated differentiation [13].
• To test this hypothesis, B16 amelanotic melanoma cell microtubules, microfilaments, or vimentin intermediate filaments were disrupted with colchicine (50 microns), cytochalasin D (50 microns), or cycloheximide (50 microns), respectively, and then cells were tail vein injected into syngeneic mice [14].
• Effect of the ionic environment on the incorporation of the intermediate-sized filament protein vimentin into residual cell structures upon treatment of Ehrlich ascites tumour cells with triton X-100. I. Biochemical analysis [15].

Biological context of Vim

• The lack of desmin was not compensated by an upregulation of vimentin in these mice either during development or regeneration [16].
• At gestation day (g.d.) 9 a single layer of vimentin filament containing cells in the myotome domain of cervical somites begins to stain positively for myogenic proteins [17].
• Amino acid sequence comparisons with other species revealed high sequence conservation of mouse vimentin to hamster (98.7%), human (96%), and chicken (88%) protein [18].
• The nucleotide sequence extends 1800 base pairs and contains the 466 amino acid mouse vimentin polypeptide chain, flanked by 90 base pairs 5' and 312 base pairs 3' untranslated region [18].
• Computer sequence analysis also revealed domains of significant homology between different alpha helical regions of vimentin and the DNA binding-leucine zipper domain of several proto-oncogenes and transcription regulators [18].

Anatomical context of Vim

• However, the vessels traversed the ILM and penetrated the vitreous body less frequently than in wild-type retinas (31-55% in Vim(-/-), 66-79% in GFAP(-/-) Vim(-/-)) [19].
• Vimentin, still present together with desmin in the myoblasts, is lost from the myotubes [17].
• We report that the intermediate filament protein vimentin is differentially regulated by these lymphokines [20].
• We used mice with targeted mutations in the GFAP or vimentin genes, or both, to study the impact of loss of either or both of these proteins on intermediate filament formation in cultured astrocytes and in normal or reactive astrocytes in vivo [21].
• Analysis of glial fibrillary acidic protein (GFAP) and vimentin in mouse lens epithelial cells (MLEC) during ontogenesis revealed a two-step developmental expression similar to that observed in astrocytes [22].

Associations of Vim with chemical compounds

• Altered taurine release following hypotonic stress in astrocytes from mice deficient for GFAP and vimentin [23].
• The cells migrating away from these explants were shown by immunocytochemistry to express vimentin and an epitope of the I antigen recognised by the antibody C6, both of which are present on the newly emerged mesoderm and not on the embryonic ectoderm in sections of embryos in utero [24].
• Finally, in vivo administration of bosentan, an endothelin receptor antagonist, totally prevented lethality in Vim-/- mice [3].
• The intermediate filament protein vimentin is a new target for epigallocatechin gallate [25].
• In addition, both heat and cadmium produced an increase in the amount of the intermediate filament protein vimentin, as determined by immunoblot and immunofluorescence assays [26].

Physical interactions of Vim

• Among these proteins, vimentin and pyruvate kinase have not been shown to bind to Fyn [27].
• A fimbrin-binding site was identified in the NH(2)-terminal domain of vimentin and the vimentin binding site at residues 143-188 in the CH1 domain of fimbrin [28].

Enzymatic interactions of Vim

• In vitro analyses revealed that Aurora-B phosphorylates vimentin at approximately 2 mol phosphate/mol of substrate for 30 min and that this phosphorylation dramatically inhibits vimentin filament formation [29].
• Protein kinase C is a serine threonine kinase which phosphorylates vimentin and through this mechanism causes intermediate filament disassembly [30].
• Vimentin and tubulin beta-chain have been reported to be phosphorylated at tyrosine residues and involved in the signal transduction pathway induced by TNF-alpha [31].
• This 50-kDa product was highly phosphorylated as compared to the bulk of the normal 55-kDa form of vimentin [32].

Co-localisations of Vim

• Immunohistochemical staining of fibroblast cultures derived from the transgenic mice with antibodies specific for vimentin and desmin demonstrated that the pVVim2 protein is assembled into filaments that co-localize with the endogenous vimentin filaments [33].
• Nestin was visualized in the platelet endothelial cell adhesion molecule and alpha smooth muscle actin-positive blood vessels and colocalized with vimentin in the interstitium [34].
• In addition, a band in erythrocyte cytoskeletons comigrates in SDS-polyacrylamide gels with vimentin isolated from mouse kidney [35].

Regulatory relationships of Vim

• Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process [29].
• We have demonstrated that keratin 14 (K14) is expressed together with vimentin in undifferentiated RLE cells [36].
• In monolayer culture, 90% of the streptozotocin-treated pancreatic cells co-expressed cytokeratin-19 and vimentin at 2 weeks and 60% expressed nestin at 4 weeks [37].
• In comparison, the astrocytes co-expressing GFAP and vimentin and those expressing exclusively GFAP, occupied regions progressively farther from the lesion site [38].
• Bfsp2 mutation found in mouse 129 strains causes the loss of CP49 and induces vimentin-dependent changes in the lens fibre cell cytoskeleton [39].

Other interactions of Vim

• In embryonic stages, E9-12, anti-ELF localized to the primary brain vesicular cells that also labeled strongly with anti-nestin but not anti-vimentin [40].
• The co-expression of mesenchymal marker alpha-smooth muscle (alpha-SMA), fibronectin and vimentin with E-cadherin in these dermal cells was further examined [41].
• Further analysis revealed several domains of significant similarity (50%) between all alpha-helices of the rod domain of vimentin and the N-terminal (approximately 210 residues) activation domain tpr of the oncogenic raf [18].
• K8, K19, and vimentin were undetectable in both lines [42].
• No differences were observed in E-cadherin and vimentin immunostain in palatal epithelium between the strains [43].

Analytical, diagnostic and therapeutic context of Vim

• Immunoblotting, immunofluorescence, and immunogold labeling analysis confirmed the absence of vimentin and of the corresponding filament network [8].
• The identification was confirmed by Western blot analysis using an anti-vimentin antibody [25].
• The chromosomal location of the mouse gene coding for vimentin, one of the intermediate filament subunits, was determined by in situ hybridization using specific H3-labelled DNA probes [44].
• In order to substantiate this idea in a tractable in vitro system, primary embryo fibroblasts from wildtype (V(+/+)) and vimentin-knockout (V(-/-)) mice were compared with regard to their growth behavior under the pseudophysiologic conditions of conventional cell culture [45].
• Atomic force microscopy (AFM) was used to study the morphology of vimentin intermediate filaments (IFs) and their assembly intermediates [46].

References