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Myosin-dependent targeting of transmembrane proteins to neuronal dendrites

Nature Neuroscience volume 12, pages 568576 (2009) | Download Citation

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Abstract

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.

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Acknowledgements

The TfR-GFP and JPA5-CD8 (G. Banker, Oregon Health Sciences University), NLG-HA (M. Silverman, Simon Fraser University), GluR1-GFP (R. Malinow, University of California at San Diego) and siRNA vector (J. Esteban, University of Michigan) plasmids and the antibodies to GluR1 (R. Wenthold, US National Institutes of Health–National Institute on Deafness and Other Communication Disorders) and EAAT3 (S. Amara, University of Pittsburgh) were gifts. The authors would like to thank E. Liman, N. Segil, D. McKemy and members of the Arnold lab for comments on the manuscript and S.H. Kwon for creating the illustrations. This work was supported by US National Institutes of Health grants NS-041963 and MH-071439 to D.B.A. and support from the Howard Hughes Medical Institute to K.S.

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Affiliations

  1. Department of Biological Sciences and Program in Molecular and Computational Biology, University of Southern California, Los Angeles, California, USA.

    • Tommy L Lewis Jr
    •  & Don B Arnold
  2. Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.

    • Tianyi Mao
    •  & Karel Svoboda

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Contributions

D.B.A. and T.L.L. designed and T.L.L. generated chimeric and mutant constructs. D.B.A. and T.L.L. designed and T.L.L. performed experiments to test constructs in dissociated neuronal cultures; K.S. and T.M. designed and performed the slice experiments; D.B.A., T.L.L., T.M. and K.S. analyzed results; D.B.A., T.L.L. and K.S. wrote the paper; and D.B.A. supervised the project.

Corresponding author

Correspondence to Don B Arnold.

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DOI

https://doi.org/10.1038/nn.2318