title: Intracellular calcium dependence of large dense-core vesicle exocytosis in the absence of synaptotagmin I.
abstract: Synaptotagmin I is a synaptic vesicle-associated protein essential for synchronous neurotransmission. We investigated its impact on the intracellular Ca(2+)-dependence of large dense-core vesicle (LDCV) exocytosis by combining Ca(2+)-uncaging and membrane capacitance measurements in adrenal slices from mouse synaptotagmin I null mutants. Synaptotagmin I-deficient chromaffin cells displayed prolonged exocytic delays and slow, yet Ca(2+)-dependent fusion rates, resulting in strongly reduced LDCV release in response to short depolarizations. Vesicle recruitment, the shape of individual amperometric events, and endocytosis appeared unaffected. These findings demonstrate that synaptotagmin I is required for rapid, highly Ca(2+)-sensitive LDCV exocytosis and indicate that it regulates the equilibrium between a slowly releasable and a readily releasable state of the fusion machinery. Alternatively, synaptotagmin I could function as calcium sensor for the readily releasable pool, leading to the destabilization of the pool in its absence.
authors.affiliation: Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany. Thomas.Voets@med.kuleuven.ac.be
authors.forename: T
authors.initials: T
authors.lastname: Voets
authors.forename: T
authors.initials: T
authors.lastname: Moser
authors.forename: P E
authors.initials: PE
authors.lastname: Lund
authors.forename: R H
authors.initials: RH
authors.lastname: Chow
authors.forename: M
authors.initials: M
authors.lastname: Geppert
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: E
authors.initials: E
authors.lastname: Neher
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D019439:Chromaffin Cells / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D050863:Synaptotagmin I; D050857:Synaptotagmins
chemical_list: D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D050857:Synaptotagmins; D002118:Calcium