Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 22; pp. 10727 - 10731
• Main Authors: Broadie, K. (University of Cambridge, Cambridge, United Kingdom), Bellen, H.J, DiAntonio, A, Littleton, J.T, Schwarz, T.L
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 25.10.1994; National Acad Sciences; National Academy of Sciences
• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.22.10727

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