Myosin-dependent targeting of transmembrane proteins to neuronal dendrites.
The distinct electrical properties of axonal and dendritic membranes are largely a result of specific transport of vesicle-bound membrane proteins to each compartment. How this specificity arises is unclear because kinesin motors that transport vesicles cannot autonomously distinguish dendritically projecting microtubules from those projecting axonally. We hypothesized that interaction with a second motor might enable vesicles containing dendritic proteins to preferentially associate with dendritically projecting microtubules and avoid those that project to the axon. Here we show that in rat cortical neurons, localization of several distinct transmembrane proteins to dendrites is dependent on specific myosin motors and an intact actin network. Moreover, fusion with a myosin-binding domain from Melanophilin targeted Channelrhodopsin-2 specifically to the somatodendritic compartment of neurons in mice in vivo. Together, our results suggest that dendritic transmembrane proteins direct the vesicles in which they are transported to avoid the axonal compartment through interaction with myosin motors.
Department of Biological Sciences, University of Southern California, Los Angeles, USA.
Tommy L
TL
Lewis
Tianyi
T
Mao
Karel
K
Svoboda
Don B
DB
Arnold
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D000075402:Channelrhodopsins; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D020409:Molecular Motor Proteins / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure
D048868:Adaptor Proteins, Signal Transducing; D000075402:Channelrhodopsins; D008565:Membrane Proteins; C435724:Mlph protein, mouse; D020409:Molecular Motor Proteins; D011993:Recombinant Fusion Proteins; D009218:Myosins