title: Structural insights into WHAMM-mediated cytoskeletal coordination during membrane remodeling.
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.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Qing-Tao
authors.initials: QT
authors.lastname: Shen
authors.forename: Peter P
authors.initials: PP
authors.lastname: Hsiue
authors.forename: Charles V
authors.initials: CV
authors.lastname: Sindelar
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Welch
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Campellone
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera
chemical_list: D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; C578123:WHAMM protein, human