title: Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis.
abstract: It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca(2+)-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Kwun Nok M
authors.initials: KN
authors.lastname: Man
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Cordelia
authors.initials: C
authors.lastname: Imig
authors.affiliation: Leibniz Institute for Molecular Pharmacology, Berlin, Germany.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Walter
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences and Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Pinheiro
authors.affiliation: Department of Physiology, Saarland University, Homburg, Germany.
authors.forename: David R
authors.initials: DR
authors.lastname: Stevens
authors.affiliation: Department of Physiology, Saarland University, Homburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences and Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jakob B
authors.initials: JB
authors.lastname: Sørensen
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Cooper
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Wojcik
mesh_terms: D000818:Animals; D019439:Chromaffin Cells / Q000378:metabolism*; D005089:Exocytosis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C485549:Unc13b protein, mouse
keywords: baiap3; docking; large dense-core vesicle; mouse; munc13; neuroendocrine; neuroscience; priming