Characterization of the role of the Synaptotagmin family as calcium sensors in facilitation and asynchronous neurotransmitter release.
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.
Saraswati
Sudipta
S
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.
Adolfsen
Bill
B
Littleton
J Troy
JT
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*
D029721:Drosophila Proteins; D018377:Neurotransmitter Agents; D050857:Synaptotagmins; D002118:Calcium
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