title: CUB and Sushi multiple domains 3 regulates dendrite development.
abstract: CUB and Sushi multiple domains 3 (CSMD3) is a large protein expressed in fetal and adult brain. Recently, mutations of the CSMD3 gene were identified in schizophrenia and autism patients. However, biochemical properties and functions of the CSMD3 protein remain unknown. Here, we demonstrate that CSMD3 is an oligomeric type I transmembrane protein localized in the apical dendrites of hippocampal pyramidal neurons in the postnatal brain. In cultured hippocampal neurons, CSMD3 is expressed only after 7 days in vitro. Overexpression of CSMD3 induced dendritic branching in hippocampal neurons. Regulation of dendritic morphology by CSMD3 depended on the presence of its extracellular region, while CSMD3 intracellular region was dispensable for this activity. These results suggest that CSMD3 acts as a co-receptor of an unidentified membrane protein to regulate dendrite development. Therefore, malfunctions of CSMD3 may be one of the factors in the pathogenesis of psychiatric disorders.
authors.affiliation: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. Electronic address: tkohno@phar.nagoya-cu.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Hattori
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C000613188:CSMD3 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
keywords: CSMD3; Neuron; Psychiatric disorder