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Originally published In Press as doi:10.1074/jbc.M311275200 on January 12, 2004

J. Biol. Chem., Vol. 279, Issue 14, 14331-14337, April 2, 2004
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MOCA Induces Membrane Spreading by Activating Rac1*

Kazuhiko Namekata, Yasushi Enokido, Kazu Iwasawa, and Hideo Kimura{ddagger}

From the National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan

The modifier of cell adhesion protein (MOCA), or Dock3, initially identified as presenilin-binding protein (PBP), belongs to the Dock180 family of proteins and is localized specifically in neurons. Here we demonstrate that MOCA binds to Rac1 and enhances its activity, which leads to the activation of c-Jun NH2-terminal kinase (JNK) and causes changes in cell morphology. Farnesylated MOCA, which is localized in the plasma membrane, enhances the activation of Rac1 and JNK more markedly than wild-type MOCA, and cells expressing farnesylated MOCA show flattened morphology similar to those expressing a constitutive active mutant of Rac1, Rac1Q61L. On poly-D-lysine-coated dishes, endogenous MOCA is concentrated on the leading edge of broad membrane protrusions (lamellipodia) where actin filaments are co-localized. MOCA is also concentrated with actin on the growth cone in primary cultures of cortical neurons. These observations suggest that MOCA may induce cytoskeletal reorganization and changes in cell adhesion by regulating the activity of Rac1.


Received for publication, October 14, 2003 , and in revised form, December 26, 2003.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan. Tel.: 81-42-346-1725; Fax: 81-42-346-1755; E-mail: kimura{at}ncnp.go.jp.


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