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Published online 2 October 2006. doi:10.1083/jcb.200605012
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 1, 135-146
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Article

Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells



Tetsuhisa Otani1,2, Tetsuo Ichii1,2, Shinya Aono1, and Masatoshi Takeichi1,2

1 Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan
2 RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan

Correspondence to Masatoshi Takeichi: takeichi{at}cdb.riken.jp

Epithelial cells are typically arranged in a honeycomb-like pattern, minimizing their cell–cell contact areas, which suggests that some tension operates for shaping of the cell boundaries. However, the molecular mechanisms that generate such tension remain unknown. We found that Tuba, which is a Cdc42-specific GEF, was concentrated at the apical-most region of cell junctions in simple epithelia via its interaction with ZO-1. RNAi–mediated depletion of Tuba altered the geometrical configuration of cell junctions, resulting in a curved and slack appearance. At the subcellular level, Tuba inactivation modified the assembly pattern of junctional F-actin and E-cadherin. Tuba RNAi also retarded cell junction formation in calcium-switch experiments. Suppression of Cdc42 activity or depletion of N-WASP, which is an effector of Cdc42, mimicked the effects of Tuba depletion. Conversely, overexpression of dominant-active Cdc42 or N-WASP enhanced the junction formation of Tuba-depleted cells. These results suggest that Tuba controls the shaping of cell junctions through the local activation of Cdc42 and its effectors.

S. Aono's present address is the Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.

Abbreviations used in this paper: AJ, adherens junction; DH, Dbl homology; GEF, guanine nucleotide exchange factor; MLC, myosin light chain; N-WASP, neural Wiskott-Aldrich syndrome protein; TJ, tight junction.


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