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増大特集 神経筋接合部―基礎から臨床まで
文献概要
はじめに
学習や記憶，情動などの脳高次機能の発現には，脳内神経回路網における適切な情報伝達が必須である。複雑な神経回路網の基本ユニットはシナプスと呼ばれる神経細胞間の接着装置であり，近年，数多くのシナプス蛋白質が同定され，それらの機能解析が行われてきた。シナプスは大きく，前シナプス，シナプス間げき，後シナプスの3つの領域に分けることができる。前シナプスには神経伝達物質を含有したシナプス小胞がクラスターを形成し，アクティブゾーン（active zone：AZ）と呼ばれる構造体にドッキングしている。活動電位の刺激によってCa2＋が神経終末に流入するとシナプス小胞は前シナプス形質膜に融合し，神経伝達物質がシナプス間げきに放出される。放出された神経伝達物質は後シナプスに存在する各種神経伝達物質受容体に結合し，後神経細胞に情報が伝達されてゆく。この一連の情報伝達の中で，AZはシナプス小胞がドッキングし融合する特異的な構造体であり，神経伝達物質の放出を時間的・空間的に制御していると考えられている。
私たちのグループは数年前に，AZに特異的な局在を示す蛋白質を精製しCAST（cytomatrix at the active zone-associated structural protein）と命名した。そのほかにも，AZ特異的蛋白質としてBassoon，Piccolo，RIM1，Munc13-1，ELKSなどが知られている。近年の生化学的なアプローチによって，これらAZ蛋白質間の相互作用と，前シナプスからの神経伝達物質放出におけるAZの役割が明らかになりつつある。本稿では，シナプス伝達の中でも特に前シナプスAZの構造と構成分子群の生理機能について，CAST/ELKSファミリーメンバーを中心に，最近の話題を提供したい。
学習や記憶，情動などの脳高次機能の発現には，脳内神経回路網における適切な情報伝達が必須である。複雑な神経回路網の基本ユニットはシナプスと呼ばれる神経細胞間の接着装置であり，近年，数多くのシナプス蛋白質が同定され，それらの機能解析が行われてきた。シナプスは大きく，前シナプス，シナプス間げき，後シナプスの3つの領域に分けることができる。前シナプスには神経伝達物質を含有したシナプス小胞がクラスターを形成し，アクティブゾーン（active zone：AZ）と呼ばれる構造体にドッキングしている。活動電位の刺激によってCa2＋が神経終末に流入するとシナプス小胞は前シナプス形質膜に融合し，神経伝達物質がシナプス間げきに放出される。放出された神経伝達物質は後シナプスに存在する各種神経伝達物質受容体に結合し，後神経細胞に情報が伝達されてゆく。この一連の情報伝達の中で，AZはシナプス小胞がドッキングし融合する特異的な構造体であり，神経伝達物質の放出を時間的・空間的に制御していると考えられている。
私たちのグループは数年前に，AZに特異的な局在を示す蛋白質を精製しCAST（cytomatrix at the active zone-associated structural protein）と命名した。そのほかにも，AZ特異的蛋白質としてBassoon，Piccolo，RIM1，Munc13-1，ELKSなどが知られている。近年の生化学的なアプローチによって，これらAZ蛋白質間の相互作用と，前シナプスからの神経伝達物質放出におけるAZの役割が明らかになりつつある。本稿では，シナプス伝達の中でも特に前シナプスAZの構造と構成分子群の生理機能について，CAST/ELKSファミリーメンバーを中心に，最近の話題を提供したい。
参考文献
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