title: Control of interneuron dendritic growth through NRG1/erbB4-mediated kalirin-7 disinhibition.
abstract: Neuregulin 1 (NRG1) is a secreted trophic factor that activates the postsynaptic erbB4 receptor tyrosine kinase. Both NRG1 and erbB4 have been repeatedly associated with schizophrenia, but their downstream targets are not well characterized. ErbB4 is highly abundant in interneurons, and NRG1-mediated erbB4 activation has been shown to modulate interneuron function, but the role for NRG1-erbB4 signaling in regulating interneuron dendritic growth is not well understood. Here we show that NRG1/erbB4 promote the growth of dendrites in mature interneurons through kalirin, a major dendritic Rac1-GEF. Recent studies have shown associations of the KALRN gene with schizophrenia. Our data point to an essential role of phosphorylation in kalirin-7's C terminus as the critical site for these effects. As reduced interneuron dendrite length occurs in schizophrenia, understanding how NRG1-erbB4 signaling modulates interneuron dendritic morphogenesis might shed light on disease-related alterations in cortical circuits.
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Cahill
authors.forename: K A
authors.initials: KA
authors.lastname: Jones
authors.forename: I
authors.initials: I
authors.lastname: Rafalovich
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: C S
authors.initials: CS
authors.lastname: Barros
authors.forename: U
authors.initials: U
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Penzes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D007395:Interneurons / Q000166:cytology* / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency* / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors; D051528:Guanylate Kinases; D008565:Membrane Proteins; D020890:Neuregulin-1; D051076:Proto-Oncogene Proteins c-fyn; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine; D020830:rac1 GTP-Binding Protein; C501447:Dlg4 protein, mouse; C548820:KALRN protein, mouse; C490581:Nrg1 protein, mouse; C524056:Erbb2 protein, mouse; C494960:Fyn protein, mouse