Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission

Synaptotagmin is an integral synaptic vesicle protein proposed to be involved in Ca2+-dependent exocytosis during synaptic transmission. Null mutations in synaptotagmin have been made in Drosophila, and the protein's in vivo function has been assayed at the neuromuscular synapse. in the absence...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-10, Vol.91 (22), p.10727-10731
Main Authors: Broadie, K. (University of Cambridge, Cambridge, United Kingdom), Bellen, H.J, DiAntonio, A, Littleton, J.T, Schwarz, T.L
Format: Article
Language:English
Subjects:
Animals
Biochemistry
CALCIO
CALCIUM
Calcium - metabolism
Calcium-Binding Proteins
CATION
CATIONES
Central nervous system
Crosses, Genetic
Drosophila
Drosophila - genetics
Drosophila - physiology
DROSOPHILA MELANOGASTER
Embryos
Ethyl Methanesulfonate
Exocytosis
Female
Genes, Lethal
Hatching
Larvae
Male
Membrane Glycoproteins - deficiency
Membrane Glycoproteins - genetics
Membrane Glycoproteins - physiology
Mutagenesis
NERF
Nerve Tissue Proteins - deficiency
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - physiology
NERVIOS
Nervous system
NEUROFISIOLOGIA
NEUROPHYSIOLOGIE
PROTEINAS
PROTEINE
Sensors
SISTEMA NERVIOSO
Synapses
Synapses - physiology
Synaptic transmission
Synaptic Transmission - physiology
Synaptic Vesicles - physiology
Synaptotagmins
SYSTEME NERVEUX
TEJIDOS ANIMALES
TISSU ANIMAL
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Summary:Synaptotagmin is an integral synaptic vesicle protein proposed to be involved in Ca2+-dependent exocytosis during synaptic transmission. Null mutations in synaptotagmin have been made in Drosophila, and the protein's in vivo function has been assayed at the neuromuscular synapse. in the absence of synaptotagmin, synaptic transmission is dramatically impaired but is not abolished. In null mutants, evoked vesicle release is decreased by a factor of 10. Moreover, the fidelity of excitation-secretion coupling is impaired so that a given stimulus generates a more variable amount of secretion. However, this residual evoked release shows Ca2+-dependence similar to normal release, suggesting either that synaptotagmin is not the Ca2+ sensor or that a second, independent Ca2+ sensor exists. While evoked transmission is suppressed, the rate of spontaneous vesicle fusion is increased by a factor of 5. We conclude that synaptotagmin is not an absolutely essential component of the Ca2+-dependent secretion pathway in synaptic transmission but is necessary for normal levels of transmission. Our data support a model in which synaptotagmin functions as a negative regulator of spontaneous vesicle fusion and acts to increase the efficiency of excitation-secretion coupling during synaptic transmission
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.22.10727