title: Necl-2/CADM1 interacts with ErbB4 and regulates its activity in GABAergic neurons.
abstract: The neuronal network is tightly regulated by a large variety of locally connected GABAergic neurons. Neuregulin1 (Nrg1) and its receptor ErbB4 are master regulators in the morphological and functional development of excitatory synapses in GABAergic neurons. We previously showed that the immunoglobulin-like cell adhesion molecule, nectin-like molecule-2 (Necl-2)/CADM1, interacts with the ErbB3 and ErbB4 receptors, and that the interaction of Necl-2 with ErbB3 inhibits the Nrg1-induced ErbB3/ErbB2 signaling in epithelial cells. Here, we examined the role of the interaction of Necl-2 with ErbB4 in GABAergic neurons. Necl-2 was co-expressed with ErbB4 in parvalbumin-positive GABAergic neurons in the mouse hippocampus and co-localized with ErbB4 at excitatory synapses. Necl-2 knockdown enhanced the Nrg1-induced phosphorylation of ErbB4. Moreover, overexpression of PTPN13, which is a tyrosine phosphatase bound to the cytoplasmic tail of Necl-2, suppressed the Nrg1-induced development of excitatory synapses in GABAergic neurons through the inhibition of ErbB4 activity. These results indicate that Necl-2 interacts with ErbB4 and regulates the development of excitatory synapses via the regulation of ErbB4 activity in GABAergic neurons.
authors.affiliation: KAN Research Institute, Kobe 650-0047, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Yamada
authors.forename: Eiji
authors.initials: E
authors.lastname: Inoue
authors.forename: Maki
authors.initials: M
authors.lastname: Deguchi-Tawarada
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Matsui
authors.forename: Aki
authors.initials: A
authors.lastname: Togawa
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ono
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000818:Animals; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D059330:GABAergic Neurons / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D066247:Receptor, ErbB-4; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D020890:Neuregulin-1; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13
keywords: CP; EC; ErbB4; GABAergic neuron; GluR1; Ig; Necl; Necl-2; Neuregulin; Nrg; Synapse; aa; amino acid; cytoplasmic tail; extracellular region; glutamate receptor 1; immunoglobulin; mAb; monoclonal antibody; nectin-like molecule; neuregulin; pAb; polyclonal antibody