Myosin VI small insert isoform maintains exocytosis by tethering secretory granules to the cortical actin

• DOI: 10.1083/jcb.201204092
• Publication Date: 2013-02-04T17:09:03Z
• Authors: Vanesa M. Tomatis; Andreas Papadopulos; Nancy T. Malintan; Sally Martin; Tristan Wallis; Rachel S. Gormal; John Kendrick-Jones; Folma Buss; Frédéric A. Meunier
• Keywords: Molecular Sequence Data; PC12 Cells; Exocytosis; Mass Spectrometry; 1307 Cell Biology; 03 medical and health sciences; Animals; Humans; Protein Isoforms; Amino Acid Sequence; Phosphorylation; Research Articles; Neurons; 0303 health sciences; Myosin Heavy Chains; Secretory Vesicles; Cell Biology; Actins; Rats; src-Family Kinases; Gene Knockdown Techniques; Calcium; Cattle; Peptides; Protein Binding

Before undergoing neuroexocytosis, secretory granules (SGs) are mobilized and tethered to the cortical actin network by an unknown mechanism. Using SG pull-down assay mass spectrometry, we found that myosin VI was recruited SGs in a Ca2+-dependent manner. Interfering with function PC12 cells reduced density of near plasma membrane without affecting their biogenesis. Myosin knockdown selectively impaired late phase exocytosis, consistent replenishment defect. This exocytic defect rescued expression small insert (SI) isoform, which efficiently network. These SI–specific effects were prevented deletion c-Src kinase phosphorylation DYD motif, identified silico. SI thus recruits network, potentially via phosphorylation, thereby maintaining active pool membrane.