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The Journal of Neuroscience, January 12, 2005, 25(2):281-290; doi:10.1523/JNEUROSCI.3692-04.2005

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Cellular/Molecular
Modifier of Cell Adhesion Regulates N-Cadherin-Mediated Cell-Cell Adhesion and Neurite Outgrowth

Qi Chen,¹ Tsan-Ju Chen,² Paul C. Letourneau,² Luciano Da F. Costa,³ and David Schubert¹

¹Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, ²Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, and ³Institute of Physics at São Carlos, São Carlos, São Paulo, Brazil

Modifier of cell adhesion (MOCA) is a member of the dedicator of cytokinesis 180 family of proteins and is highly expressed in CNS neurons. MOCA is associated with Alzheimer's disease tangles and regulates the accumulation of amyloid precursor protein and -amyloid. Here, we report that MOCA modulates cell-cell adhesion and morphology. MOCA increases the accumulation of adherens junction proteins, including N-cadherin and -catenin, whereas reducing endogenous MOCA expression lowers cell-cell aggregation and N-cadherin expression. MOCA colocalizes with N-cadherin and actin in areas of cell-cell and cell substratum contact and is expressed in neuronal processes. MOCA accumulates during neuronal differentiation, and its expression enhances NGF-induced neurite outgrowth and morphological complexity. We conclude that MOCA regulates N-cadherin-mediated cell-cell adhesion and neurite outgrowth.

Key words: adhesion; cadherin; differentiation; MOCA; nerve; neurite outgrowth

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Received June 18, 2004; revised November 10, 2004; accepted November 17, 2004.

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