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VAMP2 Binding to Munc18-1 Domain 3a Controls the Nanoscale Reorganization of the Plasma Membrane and Vesicle Interface During Vesicular Priming

49 Pages Posted: 31 Mar 2019 Last revised: 31 May 2019 Sneak Peek Status: Review Complete

See all articles by Ravikiran Kasula

Ravikiran Kasula

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Ailisa Blum

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Mercè Salla-Martret

University of Queensland, Faculty of Medicine, Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research

Ye Jin Chai

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Anmin Jiang

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Tristan P. Wallis

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Rachel S. Gormal

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Julie Z. Brouillet

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Pranesh Padmanabhan

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Saroja K. Weeratunga

University of Queensland - Institute for Molecular Bioscience

Emma K. Livingstone

University of Queensland - Institute for Molecular Bioscience

Mahdie Mollazade

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Merja Joensuu

University of Queensland - Clem Jones Centre for Ageing Dementia Research; Minerva Foundation Institute for Medical Research

Ramón Martínez-Mármol

University of Queensland, Faculty of Medicine, Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research

Brett M. Collins

University of Queensland - Institute for Molecular Bioscience

Frederic Meunier

University of Queensland - Clem Jones Centre for Ageing Dementia Research

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Abstract

SNARE-mediated secretory vesicle (SV) exocytosis underpins neuronal communication. Munc18-1 orchestrates SNARE complex formation by controlling the opening of syntaxin-1A. How the SV-plasma membrane interface becomes fusion competent at nanoscale level is unknown. Here, we propose that the interaction of Munc18-1 with VAMP2 during vesicular docking triggers nanocluster re-organization which renders the SV-plasma membrane interface fusion-competent. We identified and mutated key Munc18-1 residues (A297 and T304) in domain 3a to impair the interaction with VAMP2. This constrained SVs on the plasma membrane and reduced stimulated secretion, under rescue conditions in Munc18-1/2 double knockout neurosecretory cells. Moreover, activity-dependent de-clustering of Munc18-1 and concomitant lateral trapping of syntaxin-1A was lost. The interaction of VAMP2 with Munc18-1 domain 3a therefore controls the re-organization of the nanoscale environment of docked SV-plasma membrane interface, fostering syntaxin-1A opening and Munc18-1 release to ensure that SNARE assembly only occurs within the confinement of docked vesicles.

Suggested Citation

Kasula, Ravikiran and Blum, Ailisa and Salla-Martret, Mercè and Chai, Ye Jin and Jiang, Anmin and Wallis, Tristan P. and Gormal, Rachel S. and Brouillet, Julie Z. and Padmanabhan, Pranesh and Weeratunga, Saroja K. and Livingstone, Emma K. and Mollazade, Mahdie and Joensuu, Merja and Martínez-Mármol, Ramón and Collins, Brett M. and Meunier, Frederic, VAMP2 Binding to Munc18-1 Domain 3a Controls the Nanoscale Reorganization of the Plasma Membrane and Vesicle Interface During Vesicular Priming. Available at SSRN: https://ssrn.com/abstract=3362260 or http://dx.doi.org/10.2139/ssrn.3362260
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Ravikiran Kasula

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Ailisa Blum

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Mercè Salla-Martret

University of Queensland, Faculty of Medicine, Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Ye Jin Chai

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Anmin Jiang

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Tristan P. Wallis

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Rachel S. Gormal

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Julie Z. Brouillet

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Pranesh Padmanabhan

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Saroja K. Weeratunga

University of Queensland - Institute for Molecular Bioscience

St. Lucia
Brisbane
Australia

Emma K. Livingstone

University of Queensland - Institute for Molecular Bioscience

St. Lucia
Brisbane
Australia

Mahdie Mollazade

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Merja Joensuu

University of Queensland - Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Minerva Foundation Institute for Medical Research

Helsinki
Finland

Ramón Martínez-Mármol

University of Queensland, Faculty of Medicine, Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research

Brisbane
Australia

Brett M. Collins

University of Queensland - Institute for Molecular Bioscience

St. Lucia
Brisbane
Australia

Frederic Meunier (Contact Author)

University of Queensland - Clem Jones Centre for Ageing Dementia Research ( email )

Brisbane
Australia

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