Integrins are heterodimeric cell surface receptors for the extracellular matrix (ECM). In epithelial ceils they serve to adhere the basal surface of the cell to the basement membrane; a3b1 integrin is a receptor for laminin, a major component of basement membranes. Our studies over the past three years have identified novel roles for a3b1 integrin. However, a3b1 integrin is also found at lateral cell membranes, a location inconsistent with its function as a receptor for the ECM. We have now demonstrated that a3b1 integrin is also a component of the cadherin:catenin complex, and that the interaction of a3b1 with CD151, a member of the tetraspanin family, is required to stimulate cadherin-mediated cell-cell adhesion. We now propose to examine the significance of the integrin:tetraspanin interaction in vivo during kidney development. We have also derived a conditional mutation of the a3 integrin gene. This has been successful, and we are now breeding these mice with several Cre recombinase-expressing mice, to study the role of a3b1 integrin in specific cell types during development and tumorigenesis.
Specific Aim 1 : To study coordinate signaling mediated by a3bl integrin and associated complexes. Hypothesis: Distinct signaling pathways are activated by alternative and possibly competitive association of a3b1 integrin with the cadherin:catenin complex or with RTKs.
Specific Aim 2 : To examine the role of integrin-dependent Writ signaling in epithelial morphogenesis.
Specific Aim 3 : To determine the requirement for a3b1 integrin:tetraspanin interaction in morphogenesis of the collecting system.
| Liu, Yingjie; Chattopadhyay, Nibedita; Qin, Shan et al. (2009) Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis. Development 136:843-53 |
| Chattopadhyay, Nibedita; Wang, Zemin; Ashman, Leonie K et al. (2003) alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion. J Cell Biol 163:1351-62 |
