title: The adhesion protein IgSF9b is coupled to neuroligin 2 via S-SCAM to promote inhibitory synapse development.
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 super-resolution 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.
authors.affiliation: Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 305-701, South Korea.
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Woo
authors.forename: Seok-Kyu
authors.initials: SK
authors.lastname: Kwon
authors.forename: Jungyong
authors.initials: J
authors.lastname: Nam
authors.forename: Seungwon
authors.initials: S
authors.lastname: Choi
authors.forename: Hideto
authors.initials: H
authors.lastname: Takahashi
authors.forename: Dilja
authors.initials: D
authors.lastname: Krueger
authors.forename: Joohyun
authors.initials: J
authors.lastname: Park
authors.forename: Yeunkum
authors.initials: Y
authors.lastname: Lee
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Bae
authors.forename: Dongmin
authors.initials: D
authors.lastname: Lee
authors.forename: Jaewon
authors.initials: J
authors.lastname: Ko
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Craig
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology*; D061251:Primary Cell Culture; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C098003:neuroligin 2; D051528:Guanylate Kinases; C405684:Magi2 protein, mouse