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Molecular and cellular neurosciences v.84, 2017년, pp.100 - 111   SCI SCIE SCOPUS
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ENA/VASP proteins regulate exocytosis by mediating myosin VI-dependent recruitment of secretory granules to the cortical actin network

Tomatis, Vanesa M. (Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia ) ; Josh, Peter (Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia ) ; Papadopulos, Andreas (Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia ) ; Gormal, Rachel S. (Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia ) ; Lanoue, Vanessa (Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia ) ; Martin, Sally (Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia ) ; Meunier, Frédéric A. (Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Queensland 4072, Australia ) ;

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    Abstract In neurosecretory cells, myosin VI associated with secretory granules (SGs) mediates their activity-dependent recruitment to the cortical actin network and is necessary to sustain exocytosis. The mechanism by which myosin VI interacts with SGs is unknown. Using a myosin VI pull-down assay and mass spectrometry we identified Mena, a member of the ENA/VASP family, as a myosin VI binding partner in PC12 cells, and confirmed that Mena colocalized with myosin VI on SGs. Using a knock-sideways approach to inactivate the ENA/VASP family members by mitochondrial relocation, we revealed a concomitant redistribution of myosin VI. This was ensued by a reduction in the association of myosin VI with SGs, a decreased SG mobility and density in proximity to the plasma membrane as well as decreased evoked exocytosis. These data demonstrate that ENA/VASP proteins regulate SG exocytosis through modulating the activity of myosin VI. Highlights Mena is a secretory granule-localized myosin VI binding partner. ENA/VASP proteins target myosin VI to secretory granules. ENA/VASP proteins regulate the tethering function of myosin VI during exocytosis.


  • 주제어

    Myosin VI .   ENA/VASP proteins .   Mena .   Secretory granules .   Tethering .   Cortical actin network.  

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