Erbin controls dendritic morphogenesis by regulating localization of delta-catenin.
The LAP [leucine-rich and postsynaptic density-95/Discs large/zona occludens-1 (PDZ)] protein erbin and delta-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 delta-catenin severely impaired dendritic morphogenesis in hippocampal neurons. Simultaneous loss of erbin and delta-catenin does not enhance severity of this phenotype. The dendritic phenotype observed after erbin depletion is rescued by overexpression of delta-catenin and requires a domain in delta-catenin that has been shown to regulate dendritic branching. Knockdown of delta-catenin cannot be rescued by overexpression of erbin, indicating that erbin is upstream of delta-catenin. delta-Catenin-null neurons have no alterations in global levels of active Rac1/RhoA. Knockdown of erbin results in alterations in localization of delta-catenin. These results suggest a critical role for erbin in regulating dendritic morphogenesis by maintaining appropriate localization of delta-catenin.
Arikkath
Jyothi
J
Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA. louis.reichardt@ucsf.edu
Israely
Inbal
I
Tao
Yanmei
Y
Mei
Lin
L
Liu
Xin
X
Reichardt
Louis F
LF
D000367:Age Factors; D020816:Amino Acid Motifs; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D051381:Rats; D014162:Transfection / Q000379:methods; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D051178:alpha Catenin; C517630:erbin protein, rat; D049452:Green Fluorescent Proteins