title: Activity-driven relaxation of the cortical actomyosin II network synchronizes Munc18-1-dependent neurosecretory vesicle docking.
abstract: In neurosecretory cells, secretory vesicles (SVs) undergo Ca(2+)-dependent fusion with the plasma membrane to release neurotransmitters. How SVs cross the dense mesh of the cortical actin network to reach the plasma membrane remains unclear. Here we reveal that, in bovine chromaffin cells, SVs embedded in the cortical actin network undergo a highly synchronized transition towards the plasma membrane and Munc18-1-dependent docking in response to secretagogues. This movement coincides with a translocation of the cortical actin network in the same direction. Both effects are abolished by the knockdown or the pharmacological inhibition of myosin II, suggesting changes in actomyosin-generated forces across the cell cortex. Indeed, we report a reduction in cortical actin network tension elicited on secretagogue stimulation that is sensitive to myosin II inhibition. We reveal that the cortical actin network acts as a 'casting net' that undergoes activity-dependent relaxation, thereby driving tethered SVs towards the plasma membrane where they undergo Munc18-1-dependent docking.
authors.affiliation: The Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Papadopulos
authors.affiliation: Division of Molecular Cell Biology Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Gomez
authors.affiliation: The Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Sally
authors.identifier: 0000000192945404
authors.initials: S
authors.lastname: Martin
authors.affiliation: Molecular and Cellular Neuroscience Laboratory, Department of Human Physiology, Flinders University, Adelaide, South Australia 5159, Australia.
authors.forename: Jade
authors.initials: J
authors.lastname: Jackson
authors.affiliation: The Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Gormal
authors.affiliation: Molecular and Cellular Neuroscience Laboratory, Department of Human Physiology, Flinders University, Adelaide, South Australia 5159, Australia.
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Keating
authors.affiliation: Division of Molecular Cell Biology Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Alpha S
authors.initials: AS
authors.lastname: Yap
authors.affiliation: The Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Frederic A
authors.initials: FA
authors.lastname: Meunier
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D019439:Chromaffin Cells / Q000502:physiology*; D006576:Heterocyclic Compounds, 4 or More Rings; D051938:Munc18 Proteins / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism*; D009489:Neurosecretion; D016716:PC12 Cells; D051381:Rats; D022142:Secretory Vesicles / Q000502:physiology*
chemical_list: D000199:Actins; D006576:Heterocyclic Compounds, 4 or More Rings; D051938:Munc18 Proteins; C472645:blebbistatin; D024462:Myosin Type II