Myosin VI has a One Track Mind Versus Myosin Va When Moving on Actin Bundles or at an Intersection |
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Authors: | M. Yusuf Ali Samantha B. Previs Kathleen M. Trybus H. Lee Sweeney David M. Warshaw |
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Affiliation: | 1. Department of Molecular Physiology and Biophysics, University of Vermont, , Burlington, VT, 05405 USA;2. Department of Physiology, University of Pennsylvania School of Medicine, , Philadelphia, PA, 19104‐6085 USA;3. Pennsylvania Muscle Institute, University of Pennsylvania School of Medicine, , Philadelphia, PA, 19104‐6085 USA |
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Abstract: | Myosin VI (myoVI) and myosin Va (myoVa) serve roles both as intracellular cargo transporters and tethers/anchors. In both capacities, these motors bind to and processively travel along the actin cytoskeleton, a network of intersecting actin filaments and bundles that present directional challenges to these motors. Are myoVI and myoVa inherently different in their abilities to interact and maneuver through the complexities of the actin cytoskeleton? Thus, we created an in vitro model system of intersecting actin filaments and individual unipolar (fascin‐actin) or mixed polarity (α‐actinin‐actin) bundles. The stepping dynamics of individual Qdot‐labeled myoVI and myoVa motors were determined on these actin tracks. Interestingly, myoVI prefers to stay on the actin filament it is traveling on, while myoVa switches filaments with higher probability at an intersection or between filaments in a bundle. The structural basis for this maneuverability difference was assessed by expressing a myoVI chimera in which the single myoVI IQ was replaced with the longer, six IQ myoVa lever. The mutant behaved more like myoVI at actin intersections and on bundles, suggesting that a structural element other than the lever arm dictates myoVI's preference to stay on track, which may be critical to its role as an intracellular anchor . |
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Keywords: | anchor cargo transporter cytoskeleton molecular motors processivity Qdot single molecule tether |
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