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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK057604-09
Application #
7569014
Study Section
Special Emphasis Panel (ZRG1-RUS-B (03))
Program Officer
Hoshizaki, Deborah K
Project Start
2000-04-01
Project End
2011-01-31
Budget Start
2009-02-01
Budget End
2011-01-31
Support Year
9
Fiscal Year
2009
Total Cost
$353,335
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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