Disease relevance of BETA3

• The beta 3 subunit contributes to define ganglion cell identity in retina and its promoter, whose activation is an early marker of ganglion cell differentiation, is under the specific control of the chick atonal homolog ATH5 [1].
• However, during early mouse embryogenesis and in contrast to the chick, the beta3 integrin gene was expressed in the foregut diverticulum and in the heart and not in the cephalic neural crest cells [2].
• Increased invasive potential and up-regulation of MMP-2 in MDA-MB-231 breast cancer cells expressing the beta3 integrin subunit [3].

High impact information on BETA3

• Here we report the crystal structure of the principal integrin binding and activating fragment of talin, alone and in complex with fragments of the beta 3 integrin tail [4].
• The role of transforming growth factor beta-2, beta-3 in mediating apoptosis in the murine intestinal mucosa [5].
• Other activating mutations map to the front of the catalytic domain in the loop preceding the alphaC-helix (beta3/alphaC loop) [6].
• Results using function-blocking antibodies also demonstrate that on these cells, additional receptors for vitronectin are formed by alpha v beta 3 and alpha v associated with an unidentified 100-kD beta subunit [7].
• Although these findings are consistent with functional interchangeability of beta-tubulin isotypes, we have also found that in vivo microtubules enriched in c beta 3 polypeptides are more sensitive to cold depolymerization than those enriched in c beta 6 [8].

Biological context of BETA3

• Our experimental system exploits the properties of the promoter for the beta 3 subunit of the neuronal acetylcholine receptors, important components of various phenotypes in the CNS of vertebrates [1].
• Sequence and expression of the chicken beta 3 tubulin gene. A vertebrate testis beta-tubulin isotype [9].
• We report the determination of the complete DNA sequence for c beta 3, a chicken beta-tubulin gene which we show to be the dominant beta-tubulin expressed in testis [9].
• The beta 3 gene consists of six protein-encoding exons and the deduced protein has the structural features found in all other members of the neuronal nicotinic acetylcholine receptor subunit family [10].
• Characterization of the nicotinic acetylcholine receptor beta 3 gene. Its regulation within the avian nervous system is effected by a promoter 143 base pairs in length [10].

Anatomical context of BETA3

• The beta 3 mRNA is present in overwhelming amounts in RNA from chicken testis suggesting that this gene encodes a flagellar or meiotic spindle tubulin [11].
• Further, examination of developing chicken erythrocytes reveals that both beta-tubulins that are expressed in these cells (c beta 6 and c beta 3) are found as co-polymers of the two isoforms [8].
• We have investigated the nature of immediate cell signals produced by occupancy of the chicken osteoclast alpha v beta 3 integrin [12].
• Beta 3 is expressed in the proximal and distal regions of the developing trigeminal ganglion, i.e. in both placode- and neural crest-derived neurons [10].
• Transient transfection assays in cells freshly dissociated from selected regions of the central nervous system at different developmental stages allowed the identification of genetic elements involved in the neuronal-selective expression of the beta 3 gene [10].

Associations of BETA3 with chemical compounds

• Most importantly, induction of alpha v mRNA by 1,25-(OH)2D3 was mirrored by higher levels of expression of alpha v beta 3 on the cell surface, as well enhanced attachment to its substrate, vitronectin [13].
• The changes in cytosolic Ca2+ required the Arg-Gly-Asp sequence and were blocked by a monoclonal antibody to the alpha v beta 3 integrin, LM609 [12].
• Consistent with evidence that the beta 3 subunit regulates heterodimer expression, the sex steroid does not impact alpha v mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
• Estrogen enhances alpha v beta 3 integrin expression by avian osteoclast precursors via stabilization of beta 3 integrin mRNA [14].
• These findings demonstrate a mechanism for rapid generation of cell signals upon matrix protein binding to alpha v beta 3, which resembles the mechanisms used by tyrosine kinase growth factor receptors [15].

Physical interactions of BETA3

• We have shown that osteopontin binding to integrin alphav beta3 in osteoclasts stimulates gelsolin-associated phosphatidylinositol (PtdIns) 3-hydroxyl kinase (PI 3-kinase), leading to increased levels of gelsolin-bound PtdIns 3,4-P2, PtdIns 4,5-P2, and PtdIns 3, 4,5-P3, uncapping of barbed end actin, and actin filament formation [16].

Regulatory relationships of BETA3

• Here, talin-induced perturbations of beta3 NMR resonances were examined to explore integrin activation mechanisms [17].

Other interactions of BETA3

• The combination of insulin and FGF2 caused postmitotic Muller glia to transiently increase their expression of vimentin and putative neuron specific filamentous proteins such as neurofilament, beta3 tubulin and RA4 [18].
• These and other results suggest that TGF-beta 2 and beta 3 may play important roles and act through both autocrine and paracrine mechanisms in the development of many tissues in the chicken [19].
• We have shown previously that attachment of osteoclasts to bone and subsequent resorption are mediated by the integrin alpha v beta 3 [13].
• Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts [12].
• The neurons derived from NPE cells express neurofilament, beta3 tubulin, RA4, calretinin, Islet1, or Hu, and a few produced long axonal projections, several millimeters in length that extend across the ciliary body [20].

Analytical, diagnostic and therapeutic context of BETA3

• In situ hybridization and immunohistochemical analysis demonstrated that in retina, beta 3 transcripts and protein are confined to subpopulations of cells in the inner nuclear and ganglion cell layers [10].
• Northern blots of total RNA revealed that osteoclasts expressed the mRNA for TGF-beta 2, beta 3, and beta 4 [21].
• Western blot analyses of the purified receptors confirmed the presence of the alpha3, beta3, beta2, and beta4 subunits, and the absence of the alpha4, alpha5, and alpha7 subunits [22].
• The first immunofluorescence signal detected with specific antibodies against the beta 2 and beta 3-subunits of the GABAA receptor, the glycine receptor, and gephyrin appeared at embryonic day 12 [23].
• Immunoprecipitation studies using anti-beta3 antibodies did not detect any specific alpha-bungarotoxin labeled receptors, thus, indicating that the beta3 subunit is not present in the alpha-bungarotoxin receptors of these areas [24].

References