Myosin-X and myosin-XIX in intracellular transport Public Deposited
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- Last Modified
- March 22, 2019
DiVito, Melinda M.
- Affiliation: School of Medicine, Department of Cell Biology and Physiology
- Myosin motor proteins travel along actin filaments and power the movements responsible for force generation, vesicle and organelle trafficking, and formation of protrusive cellular structures. This dissertation discusses myosin‐X and the novel myosin‐XIX. Myosin‐X is a MyTH4‐FERM myosin that localizes to the tips of the slender, actin‐based cellular protrusions known as filopodia. Moreover, it undergoes intrafilopodial motility and is a master regulator of filopodia formation. Previously, we demonstrated that through its FERM domain, myosin‐X binds to β‐integrins. Here we describe experiments designed to elucidate the functional consequence of the myosin‐ X‐β‐integrin interaction. We report that: 1) knock‐down of myosin‐X inhibits cell spreading and adhesion, 2) the FERM domain of myosin‐X, unlike that of talin, does not activate integrins, and 3) myosin‐X co‐transports with integrins in filopodia. These results support a model in which myosin‐X is a component of the filopodia tip complex and participates in the intrafilopodial transport of other tip proteins. Myosin‐XIX is the founding member of a novel class of myosins and is the last uncharacterized human myosin. Here we report that myosin‐XIX is expressed in many cell types and shows striking localization to mitochondria. Additionally, over‐expression of a GFP‐tagged myosin‐XIX results in a dramatic gain of function phenotype in which mitochondria become hyper‐motile. To reveal the endogenous function of myosin‐XIX, we designed and tested a series of siRNAs against myosin‐XIX. With this tool, we can further characterize the function of myosin‐XIX, the first vertebrate myosin shown to localize to the mitochondria. These studies advance our understanding of the role of myosin‐X in filopodia and provide the first report of the mitochondria‐associated myosin‐XIX.
- Date of publication
- May 2010
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- ... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Cell and Molecular Physiology.
- Cheney, Richard
This work has no parents.
|Myosin-X and myosin-XIX in intracellular transport||2019-04-09||Public||