title: Calsyntenins function as synaptogenic adhesion molecules in concert with neurexins.
abstract: Multiple synaptic adhesion molecules govern synapse formation. Here, we propose calsyntenin-3/alcadein-β as a synapse organizer that specifically induces presynaptic differentiation in heterologous synapse-formation assays. Calsyntenin-3 (CST-3) is highly expressed during various postnatal periods of mouse brain development. The simultaneous knockdown of all three CSTs, but not CST-3 alone, decreases inhibitory, but not excitatory, synapse densities in cultured hippocampal neurons. Moreover, the knockdown of CSTs specifically reduces inhibitory synaptic transmission in vitro and in vivo. Remarkably, the loss of CSTs induces a concomitant decrease in neuron soma size in a non-cell-autonomous manner. Furthermore, α-neurexins (α-Nrxs) are components of a CST-3 complex involved in CST-3-mediated presynaptic differentiation. However, CST-3 does not directly bind to Nrxs. Viewed together, these data suggest that the three CSTs redundantly regulate inhibitory synapse formation, inhibitory synapse function, and neuron development in concert with Nrxs.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Um
authors.affiliation: Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan; Division of Cerebral Structure, Department of Cerebral Research, National Institute for Physiological Sciences, Okazaki 444-8787, Japan.
authors.forename: Gopal
authors.initials: G
authors.lastname: Pramanik
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Ji Seung
authors.initials: JS
authors.lastname: Ko
authors.affiliation: Department of Physiology and Neuroscience, Kyung Hee University School of Medicine, Seoul 130-701, Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Song
authors.affiliation: Department of Anatomy and Neuroscience, Korea 21 Biomedical Science, College of Medicine, Korea University, 126-1, 5-ka, Anam-dong, Seongbuk-gu, Seoul 136-705, Korea.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Neuroscience, Korea 21 Biomedical Science, College of Medicine, Korea University, 126-1, 5-ka, Anam-dong, Seongbuk-gu, Seoul 136-705, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Physiology and Neuroscience, Kyung Hee University School of Medicine, Seoul 130-701, Korea.
authors.forename: Kang-Sik
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.affiliation: Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan; Division of Cerebral Structure, Department of Cerebral Research, National Institute for Physiological Sciences, Okazaki 444-8787, Japan; PRESTO, Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tabuchi
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea. Electronic address: jaewonko@yonsei.ac.kr.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Ko
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011247:Pregnancy; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: C472553:CLSTN3 protein, human; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C472554:Clstn3 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins