Dr. Shinsuke Niwa

第10回発⽣生ダイナミクス分野主催セミナー The 10th Developmental Dynamics Seminar
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. Shinsuke Niwa"
Department of Biology, Stanford University
"
Tuesday, 11 th November, 2014; 11:00~12:00 2014年年11⽉月11⽇日（⽕火）11:00〜～12:00"
"
(Katahira) Life Sciences Project Research Laboratory, Lecture Room A "
⽚片平・⽣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 overtransported and mislocalized. In addition, we identified intragenic suppressor
of arl-8 in which a conserved nucleotide-binding domain is mutated. The gainof-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.
This seminar will be held in English.
本セミナーは⽣生命科学研究科単位認定セミナー（１ポイント）です。
Contact: Asako Sugimoto (杉本亜砂⼦子⽣生命科学研究科発⽣生ダイナミクス分野）
E-‐‑‒mail：[email protected] / TEL：022-‐‑‒217-‐‑‒6194

Download Report