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Neuregulin1 signaling promotes dendritic spine growth through kalirin
Author(s) -
Cahill Michael E.,
Remmers Christine,
Jones Kelly A.,
Xie Zhong,
Sweet Robert A.,
Penzes Peter
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12330
Subject(s) - dendritic spine , neuregulin 1 , erbb4 , forebrain , microbiology and biotechnology , spine (molecular biology) , neuregulin , gene knockdown , biology , signal transduction , neuroscience , gene , biochemistry , hippocampal formation , receptor tyrosine kinase , central nervous system
Abstract The biological functions of the neuregulin 1 ( NRG 1) and ERBB 4 genes have received much recent attention due to several studies showing associations between these genes and schizophrenia. Moreover, reduced forebrain dendritic spine density is a consistent feature of schizophrenia. It is thus important to understand the mechanisms whereby NRG 1 and erbB4 modulate spine morphogenesis. Here, we show that long‐term incubation with NRG 1 increases both spine size and density in cortical pyramidal neurons. NRG 1 also enhances the content of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors in spines. Knockdown of ERBB 4 expression prevented the effects of NRG 1 on spine size, but not on spine density. The effects of NRG 1 and erbB4 on spines were mediated by the Rac GEF kalirin, a well‐characterized regulator of dendritic spines. Finally, we show that environmental enrichment, known to promote spine growth, robustly enhances the levels of erbB4 protein in the forebrain. These findings provide a mechanistic link between NRG 1 signaling and spine morphogenesis.NRG1 and erbB4 increase spine size, while NRG1 activity, but not erbB4 activity, increases spine density. NRG1 also increases spine GluA1 content, and the GEF kalirin is necessary for the ability of NRG1 and erbB4 to regulate spine morphogenesis. We find that environmental enrichment, which is known to stimulate spine morphogenesis in the forebrain, increases cortical and hippocampal erbB4 expression.