Disease relevance of VIL1

• Villin expression during assembly of the brush border can be investigated using a human colon adenocarcinoma cell line HT29-18 [1].
• Intestinal metaplasia in the stomach is defined by the presence of intestine-like cells expressing enterocyte-specific markers, such as villin [2].
• Extensive in vitro proteolysis with Staphylococcus aureus V8 protease results in the production of a stable domain (apparent Mr 44000) which can be isolated due to its Ca2+-dependent interaction with G-actin bound to immobilized DNase-I, the standard procedure for the purification of villin [3].
• We raised monoclonal antibodies to villin and used them to localize it in human ileum and colon and in 22 colonic neoplasms [4].
• Presence of villin, a tissue-specific cytoskeletal protein, in sera of patients and an initial clinical evaluation of its value for the diagnosis and follow-up of colorectal cancers [5].

Psychiatry related information on VIL1

• Although individual responses to VIL were variable, there was an over-all improvement of about 1 1/2 SD in neuropsychological test performance during VIL treatment [6].

High impact information on VIL1

• The actin-binding protein villin induces microvillus growth and reorganization of the cytoskeleton in cells that do not normally produce this protein [7].
• Transfection of mutagenized villin cDNAs into CV-1 cells was used to show that a conserved, COOH-terminally located cluster of charged amino acid residues (KKEK) is crucial for the morphogenic activity of villin in vivo [7].
• Chemical cross-linking of actin to this peptide, the effects of amino acid substitutions in peptides, and the behavior of villin variants further corroborate the participation of the KKEK sequence in actin contacts [7].
• Villin lacking one actin-binding domain (113 amino acids), located at its carboxyterminal end, did not induce growth if microvilli or stress fiber disruption [8].
• The function of villin, an actin-binding protein, has been investigated by transfecting fibroblasts with cloned human cDNAs encoding wild-type villin or functional villin domains [8].

Chemical compound and disease context of VIL1

• One atypical bile duct adenoma displayed luminal immunoreactivity for villin [9].
• A supplement of the branched chain amino acids, valine, isoleucine, and leucine (VIL) was administered orally to patients with phenylketonuria, either together with unrestricted diet of natural protein or with a low phenylalanine diet [10].
• Lysis mediated by an IgG monoclonal antibody (J5) to the common acute lymphoblastic leukemia antigen (CALLA) was more sensitive to heparin inhibition than that due to an IgM antibody (VIL A1) [11].
• Value of CDX2, villin, and alpha-methylacyl coenzyme A racemase immunostains in the distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma [12].
• Cryosections of normal colon (NC), tubular and villous adenomas (TA, VA), and variably differentiated colon adenocarcinomas (CA) were immunostained with monoclonal antibodies to alpha 1-6 and alpha v, and beta 1-4 integrin subunits; select samples were stained for cytokeratin (Ck) 20 and villin [13].

Biological context of VIL1

• The amino acid sequence deduced from the cDNA sequence revealed that human villin is composed of three domains [14].
• Villin is a very early marker of cells involved in absorption and its expression is highly increased during intestinal cell differentiation [14].
• A cDNA library from a subclone HT29-18-C1 was constructed in an expression vector and a cDNA specific for human villin was isolated [1].
• The villin gene is located on chromosome 2q35-36 in humans and on chromosome 1 in mice [15].
• The human villin gene has one copy per haploid genome, encompasses about 25 kilobases, and contains 19 exons [15].

Anatomical context of VIL1

• Villin is a calcium-regulated actin-binding protein that caps, severs, and bundles actin filaments in vitro [14].
• We propose that it may also be related to the subcellular localization of villin in different epithelial cell types [14].
• Villin is a major protein of the microvillus cytoskeleton which binds both G and F actin in a calcium-dependent manner [16].
• Tropomyosin distinguishes between the two actin-binding sites of villin and affects actin-binding properties of other brush border proteins [17].
• The two villin mRNA species are co-expressed in normal human small and large intestinal mucosa and tumoral HT29-18 cells as well as in normal kidney [1].

Associations of VIL1 with chemical compounds

• We have previously shown that villin is tyrosine phosphorylated at four major sites [18].
• To further investigate the role of tyrosine phosphorylated villin in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) in HeLa cells [18].
• Since acid is a major component of refluxate, we investigated its effects ex vivo on cell differentiation as determined by villin expression; and on cell proliferation, as determined by tritiated thymidine incorporation and proliferating cell nuclear antigen expression [19].
• Villin is localized in the brush border of normal ileum and in the luminal border of normal colon and is expressed with increasing staining intensity as cells migrate from crypt to surface [4].
• In contrast, when stably adapted to normally lethal concentrations of methotrexate (10(-6)-10(-5) M), they form a monolayer of gobletlike cells (Lesuffleur et al., 1990) which secrete large quantities of mucins and display a discrete brush border with the presence of villin, dipeptidylpeptidase-IV, and carcinoembryonic antigen [20].

Physical interactions of VIL1

• The C-terminal actin-binding site in the ERM proteins and the actin-binding helix in the villin headpiece have a common amino acid motif [21].
• We have employed a structure-based design to construct a small folding domain from the F-actin bundling protein villin that contains the amino acids necessary for the DNA binding of the basic leucine zipper protein GCN4 and have compared its DNA binding with GCN4 [22].

Enzymatic interactions of VIL1

• Changing all of these sites to phenylalanine resulted in a villin mutant that neither was phosphorylated in TKX1 cells nor was a substrate for c-src kinase in an in vitro kinase assay [23].
• Recombinant villin was phosphorylated in vitro by the nonreceptor tyrosine kinase c-src or by expression in the TKX1 competent cells that carry an inducible tyrosine kinase gene [24].

Regulatory relationships of VIL1

• The results show that all 40 (100%) colorectal adenocarcinomas expressed CDX2 and 39 (98%) expressed villin [12].
• This inhibitor abolished the HGF-induced increase in villin levels before, but not after, confluence [25].

Other interactions of VIL1

• The difficulties observed for LDHA and VIL1 are probably due to the fact that these genes belong to large gene families and therefore suggest that they may not be the most appropriate markers for a standardisation effort [26].
• We observed inducible binding of Elk-1 and the SRF after 3 and 24 h of treatment with H. pylori, suggesting that the bacteria alone are sufficient to initiate a cascade of signaling events responsible for villin expression [2].
• Some tubular formations showed signs of proximal maturation with the presence of CALLA, CD26, and even villin [27].
• This result excludes fibronectin, villin, and desmin from being the causative genes for GFD in this large kindred [28].
• In 99 individuals haplotype analysis was performed using 6 microsatellite markers spanning a > 56 cM interval in chromosome region 2q34, where fibronectin, villin, and desmin map in close proximity [28].

Analytical, diagnostic and therapeutic context of VIL1

• In this work, specific PCR systems were developed for each of the marker genes except VIL1 (see results), from either existing bovine or human sequences, and a bovine BAC library was screened to obtain the corresponding BAC clones [26].
• Functional dissection and molecular characterization of calcium-sensitive actin-capping and actin-depolymerizing sites in villin [29].
• As shown by immunofluorescence and immunogold labelings, villin is targeted to the brush border area of differentiated HT29-18 cells but remains diffusely distributed in undifferentiated ones [30].
• Microinjection of villin into cultured cells induces rapid and long-lasting changes in cell morphology but does not inhibit cytokinesis, cell motility, or membrane ruffling [31].
• In addition an ELISA has been set up to measure villin accurately in total cell extracts [30].

References