A role for Myosin VI in the localization of axonal proteins

Tommy L. Lewis, Tianyi Mao, Don B. Arnold

Research output: Contribution to journalArticle

43 Citations (Scopus)

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-enddirected 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 in mice in vivo, suggesting that it could be a useful tool for probing circuit structure and function. Together, our results indicate that myosins help shape the polarized distributions of both axonal and dendritic proteins.

Original languageEnglish (US)
Article numbere1001021
JournalPLoS Biology
Volume9
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

myosin
Myosins
Dendrites
Axons
Protein Transport
dendrites
Proteins
Neurons
proteins
axons
Membrane Proteins
neurons
Endocytosis
transmembrane proteins
myosin VI
endocytosis
membrane proteins
functional properties
Rats
engineering

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

A role for Myosin VI in the localization of axonal proteins. / Lewis, Tommy L.; Mao, Tianyi; Arnold, Don B.

In: PLoS Biology, Vol. 9, No. 3, e1001021, 03.2011.

Research output: Contribution to journalArticle

Lewis, Tommy L. ; Mao, Tianyi ; Arnold, Don B. / A role for Myosin VI in the localization of axonal proteins. In: PLoS Biology. 2011 ; Vol. 9, No. 3.
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