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 journalArticlepeer-review

62 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

Bibliographical note

Funding Information:
The authors would like to thank Dr. Peter Sonderegger (University of Zurich, Switzerland) for kindly providing the CST expression vectors and Minsoo Kang for assistance with the quantitative analyses. This work was supported by the Korea Healthcare Technology R&D Project through the Ministry for Health and Welfare Affairs, Republic of Korea ( A120590 and A120723 to J.K.); the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology ( NRF-2013R1A6A3A04061338 to J.W.U.); the Brain Research Program through the NRF funded by the Ministry of Science, ICT, and Future Planning ( 2013-035006 to H.K.); NRF , Ministry of Education, Science, and Technology ( NRF-2012R1A1A2009219 and NRF-2012-0001160 to K.-S.P.); JST PRESTO (to K.T.); the NIMH ( R37 MH052804 to T.C.S.); JSPS KAKENHI (grant numbers 25282242 , 24650183 , and 23650180 to K.T.); and the Takeda Science Foundation (to K.T.).

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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