Myosin 5c is a class V myosin that functions in secretory granule trafficking Public Deposited

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  • March 22, 2019
Creator
  • Jacobs, Damon
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
Abstract
  • Myosin motor proteins are a super family of mechanoenzymes that carry out diverse functions in plants and animals. Class V myosins power the movement of membranous organelles along tracks composed of actin filaments. Myosin Vc (Myo5c) is the third and final member of the myosin V family to be discovered. The mRNA distribution of Myo5c indicated that it is preferentially expressed in epithelial cells and glandular tissues. Initial studies in HeLa cells indicated that Myo5c was associated with an endocytic recycling compartment. Kinetic studies showed that Myo5c is a non-processive vertebrate class V myosin. These studies revealed that, unlike Myo5a and Myo5b, Myo5c is a low duty ratio motor and the rate limiting step of the ATPase cycle is in a prehydrolysis state. More recently, we began to explore the functions of Myo5c in exocrine secretion. Tissue surveys and immunoblots of rat tissues showed that Myo5c is expressed most abundantly in acinar cells and localizes to the apical domain. Our studies utilized exocrine-derived MCF-7 cells to reveal the first endogenous localization of Myo5c in human cells. Myo5c clearly labeled distinct membrane compartments consisting of puncta and long, slender tubules. Our generation of a full-length, GFP-tagged Myo5c expression construct showed that in living cells Myo5c-associated puncta and tubules exhibit differing localization, dynamics, and dependence upon the cytoskeleton. Our key results in MCF-7 cells demonstrated that Myo5c is tightly associated with secretory granules and that expression of a dominant-negative Myo5c tail disrupts the distribution of secretory granules. Furthermore, in acinar cells of the lacrimal gland, Myo5c tail partially inhibited carbachol stimulated secretion. Together these results strongly indicate that Myo5c is a unique vertebrate class V myosin with important functions in exocrine secretion.
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  • In Copyright
Advisor
  • Erickson, Ann
  • Davis, C.
  • Cheney, Richard
  • Otey, Carol
  • Anderson, James M.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2008
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