Structural insights into WHAMM-mediated cytoskeletal coordination during membrane remodeling |
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Authors: | Qing-Tao Shen Peter P. Hsiue Charles V. Sindelar Matthew D. Welch Kenneth G. Campellone Hong-Wei Wang |
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Affiliation: | 1.Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;2.Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720;3.Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269;4.Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China 100084;5.Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China 100084 |
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Abstract: | The microtubule (MT) and actin cytoskeletons drive many essential cellular processes, yet fairly little is known about how their functions are coordinated. One factor that mediates important cross talk between these two systems is WHAMM, a Golgi-associated protein that utilizes MT binding and actin nucleation activities to promote membrane tubulation during intracellular transport. Using cryoelectron microscopy and other biophysical and biochemical approaches, we unveil the underlying mechanisms for how these activities are coordinated. We find that WHAMM bound to the outer surface of MT protofilaments via a novel interaction between its central coiled-coil region and tubulin heterodimers. Upon the assembly of WHAMM onto MTs, its N-terminal membrane-binding domain was exposed at the MT periphery, where it can recruit vesicles and remodel them into tubular structures. In contrast, MT binding masked the C-terminal portion of WHAMM and prevented it from promoting actin nucleation. These results give rise to a model whereby distinct MT-bound and actin-nucleating populations of WHAMM collaborate during membrane tubulation. |
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