title: Complexin synchronizes primed vesicle exocytosis and regulates fusion pore dynamics.
abstract: ComplexinII (CpxII) and SynaptotagminI (SytI) have been implicated in regulating the function of SNARE proteins in exocytosis, but their precise mode of action and potential interplay have remained unknown. In this paper, we show that CpxII increases Ca(2+)-triggered vesicle exocytosis and accelerates its secretory rates, providing two independent, but synergistic, functions to enhance synchronous secretion. Specifically, we demonstrate that the C-terminal domain of CpxII increases the pool of primed vesicles by hindering premature exocytosis at submicromolar Ca(2+) concentrations, whereas the N-terminal domain shortens the secretory delay and accelerates the kinetics of Ca(2+)-triggered exocytosis by increasing the Ca(2+) affinity of synchronous secretion. With its C terminus, CpxII attenuates fluctuations of the early fusion pore and slows its expansion but is functionally antagonized by SytI, enabling rapid transmitter discharge from single vesicles. Thus, our results illustrate how key features of CpxII, SytI, and their interplay transform the constitutively active SNARE-mediated fusion mechanism into a highly synchronized, Ca(2+)-triggered release apparatus.
authors.affiliation: Institute for Physiology, University of Saarland, 66424 Homburg/Saar, Germany.
authors.forename: Madhurima
authors.initials: M
authors.lastname: Dhara
authors.forename: Antonio
authors.initials: A
authors.lastname: Yarzagaray
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schwarz
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Dutta
authors.forename: Chad
authors.initials: C
authors.lastname: Grabner
authors.forename: Paanteha K
authors.initials: PK
authors.lastname: Moghadam
authors.forename: Anneka
authors.initials: A
authors.lastname: Bost
authors.forename: Claudia
authors.initials: C
authors.lastname: Schirra
authors.forename: Jens
authors.initials: J
authors.lastname: Rettig
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reim
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Ralf
authors.initials: R
authors.lastname: Mohrmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Bruns
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism; D002837:Chromaffin Granules / Q000378:metabolism; D005089:Exocytosis; D007700:Kinetics; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D050600:SNARE Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D050857:Synaptotagmins / Q000378:metabolism; D033921:Vesicular Transport Proteins
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; C424133:Sytl1 protein, mouse; D033921:Vesicular Transport Proteins; C095993:complexin II; D050857:Synaptotagmins