The muscle integrin binding protein (MIBP) interacts with [alpha]7[beta]1 integrin and regulates cell adhesion and laminin matrix deposition

Integrins are [alpha][beta] transmembrane receptors that function in key cellular processes, including cell adhesion, differentiation, and extracellular matrix deposition through interactions with extracellular, membrane, and cytoplasmic proteins. We previously identified and cloned a muscle [beta]1 integrin cytoplasmic binding protein termed MIBP and found that the expression level of MIBP is critical in the decision-making process of terminal myogenic differentiation. We report here that MIBP interacts with the [alpha]7[beta]1 integrin but not the [alpha]5[beta]1 integrin in C2C12 myoblasts, suggesting an important role of integrin [alpha] chains in the regulation of the [beta]1-MIBP interaction. Furthermore, consistent with its selective binding activity toward the [alpha]7[beta]1 laminin receptor, we have found that overexpression of MIBP in C2C12 myoblasts resulted in a significant reduction of cell adhesion to laminin and inhibition of laminin matrix deposition. By contrast, neither cell adhesion to fibronectin nor fibronectin matrix deposition was significantly altered in cells overexpressing MIBP. Finally, we show that both the protein level and tyrosine phosphorylation of paxillin, a key signaling molecule involved in the cellular control of myogenic differentiation, are increased by MIBP. These results suggest that MIBP functions in the control of myogenic differentiation by regulating [alpha]7[beta]1 integrin-mediated cell interactions with laminin matrix and intracellular signaling through paxillin. Keywords: MIBP; Integrin; Laminin; Cell adhesion; Signaling