title: Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons.
abstract: Synaptotagmin-1 and -2 are known Ca(2+) sensors for fast synchronous neurotransmitter release, but the potential Ca(2+)-sensor functions of other synaptotagmins in release remain uncharacterized. We now show that besides synaptotagmin-1 and -2, only synaptotagmin-9 (also called synaptotagmin-5) mediates fast Ca(2+) triggering of release. Release induced by the three different synaptotagmin Ca(2+) sensors exhibits distinct kinetics and apparent Ca(2+) sensitivities, suggesting that the synaptotagmin isoform expressed by a neuron determines the release properties of its synapses. Conditional knockout mice producing GFP-tagged synaptotagmin-9 revealed that synaptotagmin-9 is primarily expressed in the limbic system and striatum. Acute deletion of synaptotagmin-9 in striatal neurons severely impaired fast synchronous release without changing the size of the readily-releasable vesicle pool. These data show that in mammalian brain, only synaptotagmin-1, -2, and -9 function as Ca(2+) sensors for fast release, and that these synaptotagmins are differentially expressed to confer distinct release properties onto synapses formed by defined subsets of neurons.
authors.affiliation: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas TX 75390, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mashimo
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification* / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism; D050861:Synaptotagmin II / Q000378:metabolism; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D016704:Synapsins; D050863:Synaptotagmin I; D050861:Synaptotagmin II; D050857:Synaptotagmins; D049452:Green Fluorescent Proteins; D002118:Calcium