第 7 回 発生ダイナミクス分野主催セミナー

1. 第7回　発生ダイナミクス分野主催セミナー The arf-like small GTPase ARL-8 unfolds the autoinhibition of the motor protein UNC-104/KIF1A and regulates the distribution of synaptic vesicles. Dr. ShinsukeNiwa Department of Biology, Stanford University 2014年11月11日（火）11:00〜 片平・生命科学プロジェクト研究棟　1階講義室A Summary: Axonal transport is fundamental to the neuronal morphogenesis, maintenance and functions. We have shown that disruption of axonal transport leads to neuronal diseases. Kinesin superfamily proteins (KIFs) are microtubule-dependent molecular motors that transport various membrane organelles in axon. Of them, KIF1A/UNC-104 is a molecular motor that transport synaptic vesicle precursors. While it has been suggested that KIF1A/UNC-104 is regulated by an autoinhibition mechanism, how the autoinhibition is unlocked and the physiological meaning of the regulation remain totally unknown. ARL-8 is an arf-like small GTPase that is essential for axonal transport. In arl-8 mutant, axonal transport is down regulated. We performed an unbiased genetic screening and identified constitutive active unc-104 mutants. Cellular experiments suggested that these mutations disrupted the autoinhibition of KIF1A/UNC-104 and mutant motors became constitutive active. In these autoinhibition mutants, synaptic vesicles were over-transported and mislocalized. In addition, we identified intragenic suppressor of arl-8 in which a conserved nucleotide-binding domain is mutated. The gain-of-function ARL-8 mutant strongly bound to and activated KIF1A/UNC-104 in biochemical and cell biological experiments. Thus, we suggest that the small GTPase ARL-8 activates KIF1A/UNC-104 by unfolding the autoinhibition. As some of mutated residues found in this study are conserved in other KIFs and ARL families, these mutations may be useful to study these family members. 本セミナーは生命科学研究科単位認定セミナー（１ポイント）です。 連絡先：杉本　亜砂子　（生命科学研究科　発生ダイナミクス分野） E-mail：asugimoto@m.tohoku.ac.jp / TEL：022-217-6194