2007 Fiscal Year Final Research Report Summary
Role of Rab 13 and its effector in establishing cell polarity
| Project/Area Number |
18590271
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
NISHIMURA Noriyuki The University of Tokushima, Institute of Health Biosciences, Graduate School, Associate Professor (00322719)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | Cell polarity / Tight junction / Adherens junction / Rab13 / Rab8 / JRAB / MICAL-L2 |
|---|
| Research Abstract |
Tight junction (TJ) and adherens junction (AJ) are located at the apical end of the basolateral membrane of polarized epithelial cells. During polarization, epithelial cells first form spot-like primordial AJ at the tips of the initial cell-cell contacts and develop belt-like mature AJ. In parallel with the maturation of AJ, TJ is formed at the apical side of AJ. Whereas epithelial polarization entails a complex interplay between the coordinated TJ and AJ assembly and several fundamental cellular processes, the transport of integral TJ and AJ proteins to and/or from the plasma membrane is essential for the control of TJ and AJ assembly. We previously reported that Rab 13 and a junctional Rab13-binding protein(JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) mediated the endocytic recycling of an integral TJ protein occludin and the formation of functional TJ. In the present study, we examined the role of Rab13 and JRAB/MICAL-L2 in the transport of other integral TJ and AJ proteins claudin-1 and E-cadherin to the plasma membrane. Although knockdown of Rab13 specifically inhibited claudin-1 and occludin but not E-cadherin transport, knockdown of JRAB/MICAL-L2 and expression of its Rab13-binding domain(JRAB/MICAL-L2-C)retarded claudin-1, occludin, and E-cadherin transport. We then identified Rab8 as another JRAB/MICAL-L2-C-binding protein. Knockdown of Rab8 inhibited the Rab13-independent transport of E-cadherin to the plasma membrane. Rab13 and Rab8 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the plasma membrane and recycling endosome, respectively. These results suggest that the interactions of JRAB/MICAL-L2 with Rab13 and Rab8 play a crucial role in establishing cell polarity.
|
