これまで補体C1qを介する自然免疫古典経路がシナプス除去に関与することが示唆されていたが, どのシナプスを除去するべきか時空間的な認識機構は不明であった。本研究では補体C1qだけではなく, シグナルの下流の着目の幅を広げて検討を行った。C1qに加えC1r, sを含めたC1複合体を再構成したが, 神経細胞への結合はC1q単独の場合と差異がなかった。興味深いことにC1qは特定の糖鎖パターンを認識する抗体によるシグナルと一致し, 糖鎖を切断する酵素により消失した。一方でシナプス形成の制御分子開発として, 人工的興奮性シナプス形成分子の詳細な解析を行うと同時に, シナプスを除去する分子をデザインし性状解析を行った。
It has been suggested so far that classical complement pathway initiated by complement C1q is associated to synapse elimination, but spatio-temporal mechanism how to determine whether the synapse should be pruned or not is still unclear. This research focused not only on C1q but also on the downstream of classical complement signaling. Reconstitution of C1 complex by C1q, C1r and C1s showed the binding on neurons but the binding pattern was similar to the binding of C1q on neurons, suggesting that C1q was enough to bind on neurons. Interestingly, the labeling of C1q was well colocalized with the signals detected by antibody against specific pattern of sugar chains, and was abolished by the enzyme which degraded the sugar chains. As the other topic, in order to develop novel molecules to control synapse formation, artificial excitatory synapse connector was elaborately analyzed and synapse disconnectors were also designed and analyzed about the feature such as binding specificity.

研究種目 : 若手研究(B)
研究期間 : 2014～2015
課題番号 : 26860148
研究分野 : 分子細胞生物学