1-S01-3
新しい抑制性シナプス形成分子InSyn1の同定とその機能障害による神経疾患発症の分子機序
InSyn1 regulates GABAergic inhibition via the dystroglycan complex and is required for cognitive behaviors in mice
〇上江洲 章吉1,2、ハイジ エレン2、小林 芳彦2、ガオ ユドング2、ブラッドショー タイラー3、デヴリン パトリック2、ロドリゲス ラモーナ4、タタ プリュショサマ2、ソダリング スコット1,2,3
Akiyoshi Uezu1,2, Erin Hisey2, Yoshihiko Kobayashi2, Yudong Gao2, Tyler Bradshaw3, Patrick Devlin2, Ramona Rodriguiz4, Purushothama Tata2, Scott Soderling1,2,3
1CasTag、2デューク大学、3デューク大学、4デューク大学
1CASTAG BIOSCIENCES INC., 2The Departments of Cell Biology, Duke University Medical School, 3The Departments of Neurobiology, Duke University Medical School, 4Psychiatry and Behavioral Sciences and Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University Medical School
Human mutations in the dystroglycan complex (DGC) result in not only muscular dystrophy, but also cognitive impairments. However, the molecular architecture critical for the synaptic organization of the DGC in neurons remains elusive. Here we report Inhibitory Synaptic protein 1 (InSyn1) is a critical component of the DGC whose loss alters the composition of the GABAergic synapses, excitatory/inhibitory balance in vitro and in vivo, and cognitive behavior. Association of InSyn1 with DGC subunits is required for InSyn1 synaptic localization. InSyn1 null neurons also show a significant reduction in DGC and GABA receptor distribution as well as abnormal neuronal network activity. Moreover, InSyn1 null mice exhibit elevated neuronal firing patterns in the hippocampus and deficits in fear conditioning memory. Our results support the dysregulation of the DGC at inhibitory synapses as a driver of altered neuronal network activity and specific cognitive tasks via a novel component, InSyn1.