Disease relevance of Itga6

• Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice [1].
• The epithelial-specific integrin alpha 6 beta 4 is suprabasally expressed in benign skin tumors (papillomas) and is diffusely expressed in carcinomas associated with an increase in the proliferating compartment [2].
• Abnormal expression of integrin alpha 6 beta 4 in cervical intraepithelial neoplasia [3].
• Up-regulation of VLA-6 was absent in all intestinal granulomas [4].
• In vivo videomicroscopy experiments also revealed that an inhibition of VLA-6 migratory function by MA6 resulted in a reduction in the ability of B16F1 to extravasate during hematogenous metastasis in the liver [5].

High impact information on Itga6

• To study the contribution of the integrin alpha 6 beta 4 in hemidesmosome formation and their anchoring properties, we inactivated the beta 4 gene in mice by targeted gene disruption [6].
• The integrin alpha 6 beta 4 is expressed on squamous epithelia, on subsets of endothelial cells, immature thymocytes and on Schwann cells and fibroblasts in the peripheral nervous system [6].
• Here we report that adhesion of platelets to laminin is inhibited by a rat monoclonal antibody against the integrin family member, VLA-6 [7].
• Binding assays performed on LM-coated plates showed that 10-15% of NK cells spontaneously adhere to LM, and this adhesion is mediated by VLA-6 [8].
• Antibodies against domain E3 of laminin-1 and integrin alpha 6 subunit perturb branching epithelial morphogenesis of submandibular gland, but by different modes [9].

Chemical compound and disease context of Itga6

• An epitope on VLA-6 (alpha6beta1) integrin involved in migration but not adhesion is required for extravasation of murine melanoma B16F1 cells in liver [5].

Biological context of Itga6

• Molecular cloning of cDNA for the murine integrin alpha 6 subunit from a mammary gland lambda gt11 library showed, as in man, an open reading frame encoding two variants of alpha 6, alpha 6A and alpha 6B [10].
• We describe a novel mechanism whereby the integrin alpha 6 beta 1, a laminin receptor, can affect cell motility and induce migration onto ECM substrates with which it is not engaged [11].
• The alpha 6 beta 1 (VLA-6) and alpha 6 beta 4 protein complexes: tissue distribution and biochemical properties [12].
• 3A9 and C10 cells are of the memory phenotype (CD4+, CD8-, CD44+, CD45+) and express VLA-6 abundantly [13].
• VLA-6 has been described as a major laminin receptor with roles in diverse cell functions including cell growth and differentiation [14].

Anatomical context of Itga6

• The integrin alpha 6 beta 4 is a major component of hemidesmosomes, in which it is linked to intermediate filaments [15].
• Antibody-mediated aggregation of integrin alpha 6 beta1 yielded patches that were bigger and more heterogeneous in mouse oocytes lacking CD9 [16].
• CD9 controls the formation of clusters that contain tetraspanins and the integrin alpha 6 beta 1, which are involved in human and mouse gamete fusion [16].
• The antigen defined by HM beta 1-1 was widely distributed in various mouse cell lines and HM beta 1-1 immunoprecipitated a 110-120 kDa protein common to VLA-1 and VLA-6, indicating that HM beta 1-1 recognizes the beta 1 subunit of mouse integrins [17].
• Integrin alpha 6 is also expressed in the elongating pronephric duct as well as a subset of the rhombencephalic neural crest, which will form the Schwann cells lining several cranial nerves (VII, VIII and X) [18].

Associations of Itga6 with chemical compounds

• Another possibility is that the antibodies against integrin alpha 6 and beta 1 subunit cause abnormal signalling by the integrin [19].
• Binding to laminin (or fragment E8), but not to kalinin was partially blocked by a monoclonal antibody specific for the integrin alpha 6 subunit, and only in the initial phase of adhesion [20].
• Antibodies against the E8 domain of laminin and antibodies against the alpha 6 and beta 1 chains of platelet membrane glycoprotein very late activation antigen-6 (VLA-6), completely inhibited adhesion [21].
• Calphostin C, a protein kinase C (PKC) inhibitor, markedly inhibited the enhancement of IFN-gamma mRNA expression in a dose-dependent manner, which suggested that PKC acted as a second messenger in the IFN-gamma mRNA expression mediated by the interaction of VLA-6 with LN in CTLL-2 cells [22].
• Furthermore, the anti-alpha 6 mAb OG-1, which does not inhibit the interaction between integrin alpha 6 beta 1 and LN, had no effect on the progesterone production by GC cultured on LN [23].

Other interactions of Itga6

• Variants of the alpha 6 beta 1 laminin receptor in early murine development: distribution, molecular cloning and chromosomal localization of the mouse integrin alpha 6 subunit [10].
• Herein, we investigated the expression of receptors for fibronectin [very late antigen (VLA)-4 and VLA-5] and laminin (VLA-6), known to play a role in thymocyte migration [24].
• The results suggest that DP cells are more sensitive to an uncharacterized apoptotic death signal, and that survival is supported by the interaction between VLA-6 and merosin [25].
• Immunofluorescence staining of embryonic kidneys and of organ cultures of metanephric mesenchyme demonstrated coappearance of the integrin alpha 6 subunit and the laminin A-chain in regions where nonpolarized mesenchymal cells convert into polarized epithelial cells [26].
• The up-regulated expression of VLA-4 and VLA-6 on the surface of K1735M2L5 cells was detected by flow cytometry [27].

Analytical, diagnostic and therapeutic context of Itga6

• The presence of integrin alpha 6 subunit in all epithelia of embryonic kidney was demonstrated by immunofluorescence and by in situ hybridization [19].
• Immunoprecipitation with specific monoclonal antibody identified this complex as alpha 6 beta 1 (VLA-6) [28].
• Indirect immunofluorescence staining of various follicles and corpora lutea using two known antiintegrin alpha 6 monoclonal antibodies (450-30A1 and GoH3) showed that integrin alpha 6 was expressed on granulosa and large luteal cells in a profile similar to that of the OG-1 antigen [29].
• We have used subunit-specific monoclonal antibodies (MAbs) and immunohistochemistry to examine the distribution of integrin alpha 6 beta 4 in normal ectocervical epithelium and various grades of cervical intraepithelial neoplasia (CIN) [3].
• Initially, at 1 week epithelia of benign and malignant cells revealed a similarly low polarity and an enlarged 'activated basal' compartment, reflected by partial dislocation and extended pericellular staining of the hemidesmosome constituent integrin alpha 6 beta 4 seen by immunofluorescence [30].

References