a role for myosin vi in the localization of axonal proteins肌凝蛋白的作用vi的定位轴突的蛋白质.pdfVIP

A Role for Myosin VI in the Localization of Axonal Proteins Tommy L. Lewis Jr.1,2, Tianyi Mao3¤, Don B. Arnold1,2* 1 Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America, 2 Program in Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America, 3 Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America Abstract In neurons polarized trafficking of vesicle-bound membrane proteins gives rise to the distinct molecular composition and functional properties of axons and dendrites. Despite their central role in shaping neuronal form and function, surprisingly little is known about the molecular processes that mediate polarized targeting of neuronal proteins. Recently, the plus-end- directed motor Myosin Va was shown to play a critical role in targeting of transmembrane proteins to dendrites; however, the role of myosin motors in axonal targeting is unknown. Here we show that Myosin VI, a minus-end-directed motor, plays a vital role in the enrichment of proteins on the surface of axons. Engineering non-neuronal proteins to interact with Myosin VI causes them to become highly concentrated at the axonal surface in dissociated rat cortical neurons. Furthermore, disruption of either Myosin VI function or expression leads to aberrant dendritic localization of axonal proteins. Myosin VI mediates the enrichment of proteins on the axonal surface at least in part by stimulating dendrite-specific endocytosis, a mechanism that has been shown to underlie the localization of many axonal proteins. In addition, a version of Channelrhodopsin 2 that was engineered to bind to Myosin VI is concentrated at the surface of the axon of cortical neurons