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The Journal of Neuroscience, July 9, 2008, 28(28):7047-7056; doi:10.1523/JNEUROSCI.0451-08.2008

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Cellular/Molecular
Erbin Controls Dendritic Morphogenesis by Regulating Localization of -Catenin

Jyothi Arikkath,¹ Inbal Israely,² Yanmei Tao,⁵ Lin Mei,⁵ Xin Liu,^2,3,4 and Louis F. Reichardt¹

¹Department of Physiology, University of California, San Francisco, San Francisco, California 94158, Departments of ²Molecular and Medical Pharmacology and ³Pathology and Laboratory Medicine, and ⁴Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90095, and ⁵Program of Developmental and Regenerative Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912

Correspondence should be addressed to either Louis F. Reichardt or Jyothi Arikakth, Department of Physiology, 1550 Fourth Street, University of California, San Francisco, San Francisco, CA 94158. Email: louis.reichardt{at}ucsf.edu or Email: Jyothi.arikkath{at}ucsf.edu

The LAP [leucine-rich and postsynaptic density-95/Discs large/zona occludens-1 (PDZ)] protein erbin and -catenin, a component of the cadherin–catenin cell adhesion complex, are highly expressed in neurons and associate through PDZ-mediated interaction, but have incompletely characterized neuronal functions. We show that short hairpin RNA-mediated knockdown of erbin and knockdown or genetic ablation of -catenin severely impaired dendritic morphogenesis in hippocampal neurons. Simultaneous loss of erbin and -catenin does not enhance severity of this phenotype. The dendritic phenotype observed after erbin depletion is rescued by overexpression of -catenin and requires a domain in -catenin that has been shown to regulate dendritic branching. Knockdown of -catenin cannot be rescued by overexpression of erbin, indicating that erbin is upstream of -catenin. -Catenin-null neurons have no alterations in global levels of active Rac1/RhoA. Knockdown of erbin results in alterations in localization of -catenin. These results suggest a critical role for erbin in regulating dendritic morphogenesis by maintaining appropriate localization of -catenin.

Key words: dendrite; -catenin; erbin; LAP proteins; localization; PDZ

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Received Jan. 31, 2008; revised April 2, 2008; accepted May 8, 2008.

Correspondence should be addressed to either Louis F. Reichardt or Jyothi Arikakth, Department of Physiology, 1550 Fourth Street, University of California, San Francisco, San Francisco, CA 94158. Email: louis.reichardt{at}ucsf.edu or Email: Jyothi.arikkath{at}ucsf.edu

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