Neurons are highly specialized for the processing and transmission of cellular signals.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting Information files.įunding: National Major Basic Research Program of China ( ): 2016YFA0501001 for MD and 2017YFA0503501 for WF Strategic Priority Research Program of CAS ( ): XDB37020302 for WF National Natural Science Foundation of China (NSFC) ( ): 31921002 for MD, 32071191 for WF, 32070810 for MD, 31770786 for WF, 31829001 for WF, 3140593 for MD and 31971160 for WF NIH Office of Research Infrastructure Program (P40 OD010440) for the CGC. Received: JanuAccepted: NovemPublished: November 29, 2021Ĭopyright: © 2021 Cong et al. (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.
0 kommentar(er)
