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标题：Investigations of human myosin VI targeting using optogenetically controlled cargo loading
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作者：Alexander R. French ; Tobin R. Sosnick ; Ronald S. Rock 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：9
页码：E1607-E1616
DOI：10.1073/pnas.1614716114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Myosins play countless critical roles in the cell, each requiring it to be activated at a specific location and time. To control myosin VI with this specificity, we created an optogenetic tool for activating myosin VI by fusing the light-sensitive Avena sativa phototropin1 LOV2 domain to a peptide from Dab2 (LOVDab), a myosin VI cargo protein. Our approach harnesses the native targeting and activation mechanism of myosin VI, allowing direct inferences on myosin VI function. LOVDab robustly recruits human full-length myosin VI to various organelles in vivo and hinders peroxisome motion in a light-controllable manner. LOVDab also activates myosin VI in an in vitro gliding filament assay. Our data suggest that protein and lipid cargoes cooperate to activate myosin VI, allowing myosin VI to integrate Ca²⁺, lipid, and protein cargo signals in the cell to deploy in a site-specific manner.
关键词：motor proteins ; optogenetics ; myosin VI ; LOV2 ; protein regulation