Calsyntenins Function as Synaptogenic Adhesion Molecules in Concert with Neurexins
Ji Won Um,
Gopal Pramanik,
Ji Seung Ko,
Min-Young Song,
Dongmin Lee,
Hyun Kim,
Kang-Sik Park,
Thomas C. Südhof,
Katsuhiko Tabuchi,
Jaewon Ko
Affiliations
Ji Won Um
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea
Gopal Pramanik
Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Ji Seung Ko
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea
Min-Young Song
Department of Physiology and Neuroscience, Kyung Hee University School of Medicine, Seoul 130-701, Korea
Dongmin Lee
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
Hyun Kim
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
Kang-Sik Park
Department of Physiology and Neuroscience, Kyung Hee University School of Medicine, Seoul 130-701, Korea
Thomas C. Südhof
Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
Katsuhiko Tabuchi
Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Jaewon Ko
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea
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.
