The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to promote inhibitory synapse development

Jooyeon Woo, Seok Kyu Kwon, Jungyong Nam, Seungwon Choi, Hideto Takahashi, Dilja Krueger, Joohyun Park, Yeunkum Lee, Jin Young Bae, Dongmin Lee, Jaewon Ko, Hyun Kim, Myoung Hwan Kim, Yong Chul Bae, Sunghoe Chang, Ann Marie Craig, Eunjoon Kim

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52 Citations (Scopus)

Abstract

Synaptic adhesion molecules regulate diverse aspects of synapse formation and maintenance. Many known synaptic adhesion molecules localize at excitatory synapses, whereas relatively little is known about inhibitory synaptic adhesion molecules. Here we report that IgSF9b is a novel, brain-specific, homophilic adhesion molecule that is strongly expressed in GABAergic interneurons. IgSF9b was preferentially localized at inhibitory synapses in cultured rat hippocampal and cortical interneurons and was required for the development of inhibitory synapses onto interneurons. IgSF9b formed a subsynaptic domain distinct from the GABAA receptor- and gephyrin-containing domain, as indicated by superresolution imaging. IgSF9b was linked to neuroligin 2, an inhibitory synaptic adhesion molecule coupled to gephyrin, via the multi-PDZ protein S-SCAM. IgSF9b and neuroligin 2 could reciprocally cluster each other. These results suggest a novel mode of inhibitory synaptic organization in which two subsynaptic domains, one containing IgSF9b for synaptic adhesion and the other containing gephyrin and GABAA receptors for synaptic transmission, are interconnected through S-SCAM and neuroligin 2.

Original languageEnglish
Pages (from-to)929-944
Number of pages16
JournalJournal of Cell Biology
Volume201
Issue number6
DOIs
Publication statusPublished - 2013 Jun

ASJC Scopus subject areas

  • Cell Biology

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    Woo, J., Kwon, S. K., Nam, J., Choi, S., Takahashi, H., Krueger, D., Park, J., Lee, Y., Bae, J. Y., Lee, D., Ko, J., Kim, H., Kim, M. H., Bae, Y. C., Chang, S., Craig, A. M., & Kim, E. (2013). The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to promote inhibitory synapse development. Journal of Cell Biology, 201(6), 929-944. https://doi.org/10.1083/jcb.201209132