(2021) Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A. Thus, the CC1/motor domain-mediated autoinhibition is crucial for UNC-104/KIF1A-mediated axonal transport in vivo.Ĭitation: Cong D, Ren J, Zhou Y, Wang S, Liang J, Ding M, et al. Genetically engineered mutations in the motor domain or CC1 of UNC-104, which disrupt the autoinhibitory interface, also led to the gain of function and hyperactivation of axonal transport. The gain-of-function mutation on the motor domain leads to an active dimeric conformation, releasing the inhibitory CC1 region from the motor domain. Once on the neuronal process, the mutant motors display dynamic movement similarly to wild type motors. In contrast to the cell body localization of wild type motor, the mutant motors accumulate on neuronal processes.

Here, we identified point mutations located in the motor domain or the inhibitory CC1 domain, which resulted in gain-of-function alleles of unc-104 that exhibit hyperactive axonal transport and abnormal accumulation of synaptic vesicles. The UNC-104/KIF1A motor is crucial for axonal transport of synaptic vesicles, but how the UNC-104/KIF1A motor is activated in vivo is not fully understood.

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