The LRR-TM protein PAN-1 interacts with MYRF to promote its nuclear translocation in synaptic remodeling
Shi-Li Xia,
Meng Li,
Bing Chen,
Chao Wang,
Yong-Hong Yan,
Meng-Qiu Dong,
Yingchuan B Qi
Affiliations
Shi-Li Xia
School of Life Science and Technology, ShanghaiTech University, Shanghai, China; College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
Meng Li
School of Life Science and Technology, ShanghaiTech University, Shanghai, China; College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
Bing Chen
College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
Chao Wang
College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
Yong-Hong Yan
National Institute of Biological Sciences, Beijing, China
School of Life Science and Technology, ShanghaiTech University, Shanghai, China; College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
Neural circuits develop through a plastic phase orchestrated by genetic programs and environmental signals. We have identified a leucine-rich-repeat domain transmembrane protein PAN-1 as a factor required for synaptic rewiring in C. elegans. PAN-1 localizes on cell membrane and binds with MYRF, a membrane-bound transcription factor indispensable for promoting synaptic rewiring. Full-length MYRF was known to undergo self-cleavage on ER membrane and release its transcriptional N-terminal fragment in cultured cells. We surprisingly find that MYRF trafficking to cell membrane before cleavage is pivotal for C. elegans development and the timing of N-MYRF release coincides with the onset of synaptic rewiring. On cell membrane PAN-1 and MYRF interact with each other via their extracellular regions. Loss of PAN-1 abolishes MYRF cell membrane localization, consequently blocking myrf-dependent neuronal rewiring process. Thus, through interactions with a cooperating factor on the cell membrane, MYRF may link cell surface activities to transcriptional cascades required for development.
