title: Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo.
abstract: The actin cytoskeleton plays crucial roles in many cellular processes, including regulated secretion. However, the mechanisms controlling F-actin dynamics in this process are largely unknown. Through 3D time-lapse imaging in a secreting organ, we show that F-actin is actively disassembled along the apical plasma membrane at the site of secretory vesicle fusion and re-assembled directionally on vesicle membranes. Moreover, we show that fusion pore formation and PIP2 redistribution precedes actin and myosin recruitment to secretory vesicle membranes. Finally, we show essential roles for the branched actin nucleators Arp2/3- and WASp in the process of secretory cargo expulsion and integration of vesicular membranes with the apical plasma membrane. Our results highlight previously unknown roles for branched actin in exocytosis and provide a genetically tractable system to image the temporal and spatial dynamics of polarized secretion in vivo.
authors.affiliation: Developmental Glycobiology Section, NIDCR, National Institutes of Health, Building 30, Room 426, 30 Convent Drive, MSC 4370, Bethesda, Maryland 20892, USA.
authors.forename: Duy T
authors.initials: DT
authors.lastname: Tran
authors.affiliation: Intracellular Membrane Trafficking Section, NIDCR, National Institutes of Health, 30 Convent Drive, Bethesda, Maryland 20892, USA.|Oncology Research Unit, School of Medical Sciences, University of New South Wales, Wallace Wurth Building East (C27), Room 227, Sydney, New South Wales 2052, Australia.
authors.forename: Andrius
authors.initials: A
authors.lastname: Masedunskas
authors.affiliation: Intracellular Membrane Trafficking Section, NIDCR, National Institutes of Health, 30 Convent Drive, Bethesda, Maryland 20892, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Weigert
authors.affiliation: Developmental Glycobiology Section, NIDCR, National Institutes of Health, Building 30, Room 426, 30 Convent Drive, MSC 4370, Bethesda, Maryland 20892, USA.
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Ten Hagen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005089:Exocytosis; D021621:Imaging, Three-Dimensional; D009218:Myosins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*; D059008:Time-Lapse Imaging; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D029721:Drosophila Proteins; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; D009218:Myosins