title: 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.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cahill
authors.forename: Christine
authors.initials: C
authors.lastname: Remmers
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Jones
authors.forename: Zhong
authors.initials: Z
authors.lastname: Xie
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D003432:Cross-Linking Reagents; D049229:Dendritic Spines / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D018613:Microscopy, Confocal; D020890:Neuregulin-1 / Q000494:pharmacology / Q000502:physiology*; D010957:Plasmids; D011247:Pregnancy; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D003432:Cross-Linking Reagents; D066246:ErbB Receptors; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors; D020890:Neuregulin-1; D066247:Receptor, ErbB-4; D018091:Receptors, AMPA; C102365:Kalrn protein, rat; C587691:Erbb4 protein, rat
keywords: ERBB4; NRG1; environmental enrichment; plasticity; schizophrenia; synapse