title: Myosin VI small insert isoform maintains exocytosis by tethering secretory granules to the cortical actin.
abstract: Before undergoing neuroexocytosis, secretory granules (SGs) are mobilized and tethered to the cortical actin network by an unknown mechanism. Using an SG pull-down assay and mass spectrometry, we found that myosin VI was recruited to SGs in a Ca(2+)-dependent manner. Interfering with myosin VI function in PC12 cells reduced the density of SGs near the plasma membrane without affecting their biogenesis. Myosin VI knockdown selectively impaired a late phase of exocytosis, consistent with a replenishment defect. This exocytic defect was selectively rescued by expression of the myosin VI small insert (SI) isoform, which efficiently tethered SGs to the cortical actin network. These myosin VI SI-specific effects were prevented by deletion of a c-Src kinase phosphorylation DYD motif, identified in silico. Myosin VI SI thus recruits SGs to the cortical actin network, potentially via c-Src phosphorylation, thereby maintaining an active pool of SGs near the plasma membrane.
authors: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors: Vanesa M
authors: VM
authors: Tomatis
authors: Andreas
authors: A
authors: Papadopulos
authors: Nancy T
authors: NT
authors: Malintan
authors: Sally
authors: S
authors: Martin
authors: Tristan
authors: T
authors: Wallis
authors: Rachel S
authors: RS
authors: Gormal
authors: John
authors: J
authors: Kendrick-Jones
authors: Folma
authors: F
authors: Buss
authors: Frédéric A
authors: FA
authors: Meunier
mesh_terms: D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D005089:Exocytosis; D055785:Gene Knockdown Techniques; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D010455:Peptides; D020033:Protein Isoforms; C089785:myosin VI; D019061:src-Family Kinases; D018995:Myosin Heavy Chains; D002118:Calcium
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