title: Synaptotagmin-1 and -7 are functionally overlapping Ca2+ sensors for exocytosis in adrenal chromaffin cells.
abstract: Synaptotagmin-1, the canonical isoform of the synaptotagmin family, is a Ca(2+) sensor for fast synchronous neurotransmitter release in forebrain neurons and chromaffin cells. Even though deletion of synaptotagmin-1 abolishes fast exocytosis in chromaffin cells, it reduces overall secretion by only 20% because of the persistence of slow exocytosis. Therefore, another Ca(2+) sensor dominates release in these cells. Synaptotagmin-7 has a higher Ca(2+) affinity and slower binding kinetics than synaptotagmin-1, matching the proposed properties for the second, slower Ca(2+) sensor. Here, we examined Ca(2+)-triggered exocytosis in chromaffin cells from KO mice lacking synaptotagmin-7, and from knockin mice containing normal levels of a mutant synaptotagmin-7 whose C(2)B domain does not bind Ca(2+). In both types of mutant chromaffin cells, Ca(2+)-triggered exocytosis was decreased dramatically. Moreover, in chromaffin cells lacking both synaptotagmin-1 and -7, only a very slow release component, accounting for approximately 30% of WT exocytosis, persisted. These data establish synaptotagmin-7 as a major Ca(2+) sensor for exocytosis in chromaffin cells, which, together with synaptotagmin-1, mediates almost all of the Ca(2+) triggering of exocytosis in these cells, a surprising result, considering the lack of a role of synaptotagmin-7 in synaptic vesicle exocytosis.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Schonn
authors.forename: Anton
authors.initials: A
authors.lastname: Maximov
authors.forename: Ye
authors.initials: Y
authors.lastname: Lao
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.forename: Jakob B
authors.initials: JB
authors.lastname: Sørensen
mesh_terms: D000311:Adrenal Glands / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis; D017353:Gene Deletion; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D050863:Synaptotagmin I / Q000378:metabolism*; D050857:Synaptotagmins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050863:Synaptotagmin I; D050857:Synaptotagmins; D002118:Calcium