title: Characterization of the role of the Synaptotagmin family as calcium sensors in facilitation and asynchronous neurotransmitter release.
abstract: Ca(2+) influx into presynaptic nerve terminals activates synaptic vesicle exocytosis by triggering fast synchronous fusion and a slower asynchronous release pathway. In addition, a brief rise in Ca(2+) after consecutive action potentials has been correlated with a form of short-term synaptic plasticity with enhanced vesicle fusion termed facilitation. Although the synaptic vesicle protein Synaptotagmin 1 (Syt1) has been implicated as the Ca(2+) sensor for synchronous fusion, the molecular identity of the Ca(2+) sensors that mediate facilitation and asynchronous release is unknown. To test whether the synchronous Ca(2+) sensor, Syt1, or the asynchronous Ca(2+) sensor is involved in facilitation, we analyzed whether genetic elimination of Syt1 in Drosophila results in a concomitant impairment in facilitation. Our results indicate that Syt1 acts as a redundant Ca(2+) sensor for facilitation, with the asynchronous Ca(2+) sensor contributing significantly to this form of short-term plasticity. We next examined whether other members of the Drosophila Syt family functioned in Ca(2+)-dependent asynchronous release or facilitation in vivo. Genetic elimination of other panneuronally expressed Syt proteins did not alter these forms of exocytosis, indicating a non-Syt Ca(2+) sensor functions for both facilitation and asynchronous release. In light of these findings, the presence of two presynaptic Ca(2+) sensors can be placed in a biological context, a Syt1-based Ca(2+) sensor devoted primarily to baseline synaptic transmission and a second non-Syt Ca(2+) sensor for short-term synaptic plasticity and asynchronous release.
authors: The Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Sudipta
authors: S
authors: Saraswati
authors: Bill
authors: B
authors: Adolfsen
authors: J Troy
authors: JT
authors: Littleton
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000502:physiology*; D004330:Drosophila / Q000254:growth & development / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D017353:Gene Deletion; D007814:Larva / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000502:physiology; D050857:Synaptotagmins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D018377:Neurotransmitter Agents; D050857:Synaptotagmins; D002118:Calcium
references: Neuron. 1999 Oct;24(2):363-76
references: 10571230
references: J Neurosci. 2000 Jun 15;20(12):4414-22
references: 10844010
references: Cell Mol Life Sci. 2001 Mar;58(3):393-402
references: 11315187
references: Neuron. 2001 May;30(2):459-73
references: 11395007
references: Science. 2001 Nov 2;294(5544):1111-5
references: 11691996
references: Annu Rev Physiol. 2002;64:355-405
references: 11826273
references: Neuron. 2002 Dec 5;36(5):897-908
references: 12467593
references: J Cell Biol. 2003 Aug 18;162(4):543-9
references: 12925704
references: Nature. 2003 Aug 21;424(6951):943-7
references: 12931189
references: J Biol Chem. 2003 Oct 17;278(42):41099-108
references: 12896973
references: J Neurosci. 2004 May 12;24(19):4518-29
references: 15140922
references: J Neurosci. 2004 Jul 7;24(27):6127-32
references: 15240804
references: J Cell Biol. 2004 Jul 19;166(2):249-60
references: 15263020
references: J Physiol. 1984 Jan;346:257-71
references: 6142104
references: Science. 1992 May 15;256(5059):1021-5
references: 1589771
references: Cell. 1994 Nov 18;79(4):717-27
references: 7954835
references: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12942-6
references: 7809151
references: Nature. 1995 Jun 15;375(6532):594-9
references: 7791877
references: J Physiol. 1954 Jun 28;124(3):574-85
references: 13175200
references: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5210-4
references: 15793006
references: Science. 2005 Nov 4;310(5749):858-63
references: 16272123
references: Cell. 2006 Nov 17;127(4):831-46
references: 17110340
references: J Cell Biol. 2007 Jan 1;176(1):113-24
references: 17190793