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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 invitro and invivo. 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.

Original languageEnglish
Pages (from-to)1096-1109
Number of pages14
JournalCell Reports
Volume6
Issue number6
DOIs
Publication statusPublished - 2014 Mar 27

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Um, J. W., Pramanik, G., Ko, J. S., Song, M. Y., Lee, D., Kim, H., Park, K. S., Südhof, T. C., Tabuchi, K., & Ko, J. (2014). Calsyntenins Function as Synaptogenic Adhesion Molecules in Concert with Neurexins. Cell Reports, 6(6), 1096-1109. https://doi.org/10.1016/j.celrep.2014.02.010