Neuregulin1 signaling promotes dendritic spine growth through kalirin.

Abstract

The biological functions of the neuregulin 1 (NRG1) and ERBB4 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 NRG1 and erbB4 modulate spine morphogenesis. Here, we show that long-term incubation with NRG1 increases both spine size and density in cortical pyramidal neurons. NRG1 also enhances the content of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in spines. Knockdown of ERBB4 expression prevented the effects of NRG1 on spine size, but not on spine density. The effects of NRG1 and erbB4 on spines were mediated by the RacGEF 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 NRG1 signaling and spine morphogenesis

• Authors: Michael E Cahill, Christine Remmers, Kelly A Jones, Zhong Xie, Robert A Sweet, Peter Penzes
• Journal: Journal of neurochemistry (J Neurochem) Vol. 126 Issue 5 Pg. 625-35 (Sep 2013) ISSN: 1471-4159 [Electronic] England
• PMID: 23742124 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2013 International Society for Neurochemistry

Chemical References

• Cross-Linking Reagents
• Guanine Nucleotide Exchange Factors
• Kalrn protein, rat
• Neuregulin-1
• Receptors, AMPA
• Green Fluorescent Proteins
• ErbB Receptors
• Erbb4 protein, rat
• Receptor, ErbB-4
• glutamate receptor ionotropic, AMPA 1

Topics

• Animals
• Cells, Cultured
• Cerebral Cortex (cytology, drug effects, growth & development)
• Cross-Linking Reagents
• Dendritic Spines (physiology)
• ErbB Receptors (genetics)
• Female
• Fluorescent Antibody Technique
• Green Fluorescent Proteins
• Guanine Nucleotide Exchange Factors (physiology)
• Image Processing, Computer-Assisted
• Microscopy, Confocal
• Neuregulin-1 (pharmacology, physiology)
• Plasmids
• Pregnancy
• Pyramidal Cells (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Receptor, ErbB-4
• Receptors, AMPA (biosynthesis, drug effects, genetics, physiology)
• Signal Transduction (physiology)
• Transfection