The overall goal of this research proposal is to identify the molecular switches that are involved in the assembly of intercellular junctions as a result of glucocorticoids treatment (see attached figures 1 & 2).
The specific aims of this proposal are: 1)To determine whether glucocorticoids regulate the formation of known protein complexes such as between E-cadherin and beta- catenin, beta-catenin and ZO-1, beta-catenin and fascin, and functionally test the significance of these glucocorticoid induced changes in the formation of intercellular junctions; 2) To test whether overexpression of fascin, a recently identified beta-catenin-binding protein, would inhibit glucocorticoids-induced intercellular junctions formation (my preliminary results show that fascin protein level is down regulated by glucocorticoids treatment in Con8 cells); 3)To identify downstream signals of glucocorticoids for intercellular junctions formation by testing known junctions signaling molecules such as PKC zeta, RhoA, and G alpha12 as well as to identify novel molecules that are involved in glucocorticoids-regulated protein-protein interaction(s).
| Tang, Vivian W; Goodenough, Daniel A (2003) Paracellular ion channel at the tight junction. Biophys J 84:1660-73 |
