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Vol. 19, Issue 3, 971-983, March 2008

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The Interaction of JRAB/MICAL-L2 with Rab8 and Rab13 Coordinates the Assembly of Tight Junctions and Adherens Junctions

Rie Yamamura^*,, Noriyuki Nishimura^*, Hiroyoshi Nakatsuji^*, Seiji Arase, and Takuya Sasaki^*

*Departments of Biochemistry and Dermatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan

Submitted June 11, 2007; Revised November 5, 2007; Accepted December 6, 2007
Monitoring Editor: Asma Nusrat

The assembly of tight junctions (TJs) and adherens junctions (AJs) is regulated by the transport of integral TJ and AJ proteins to and/or from the plasma membrane (PM) and it is tightly coordinated in epithelial cells. We previously reported that Rab13 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 TJs. Here, we investigated 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 PM by using a Ca²⁺-switch model. Although knockdown of Rab13 specifically suppressed 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) inhibited 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 PM. Rab8 and Rab13 competed with each other for the binding to JRAB/MICAL-L2 and functionally associated with JRAB/MICAL-L2 at the perinuclear recycling/storage compartments and PM, respectively. These results suggest that the interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of AJs and TJs.

Address correspondence to: Takuya Sasaki (sasaki{at}basic.med.tokushima-u.ac.jp)

Abbreviations used: AJ, adherens junction; CC, coiled-coil; PM, plasma membrane; siRNA, small interfering RNA; TfR, transferrin receptor; TJ, tight junction; ZO, zonula occludens.