Kinetics of synaptotagmin responses to Ca2+ and assembly with the core SNARE complex onto membranes

The synaptic vesicle protein synaptotagmin I binds Ca2+ and is required for efficient neurotransmitter release. Here, we measure the response time of the C2 domains of synaptotagmin to determine whether synaptotagmin is fast enough to function as a Ca2+ sensor for rapid exocytosis. We report that sy...

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Veröffentlicht in:Neuron (Cambridge, Mass.) Mass.), 1999-10, Vol.24 (2), p.363-376
Hauptverfasser: Davis, A F, Bai, J, Fasshauer, D, Wolowick, M J, Lewis, J L, Chapman, E R
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container_end_page 376
container_issue 2
container_start_page 363
container_title Neuron (Cambridge, Mass.)
container_volume 24
creator Davis, A F
Bai, J
Fasshauer, D
Wolowick, M J
Lewis, J L
Chapman, E R
description The synaptic vesicle protein synaptotagmin I binds Ca2+ and is required for efficient neurotransmitter release. Here, we measure the response time of the C2 domains of synaptotagmin to determine whether synaptotagmin is fast enough to function as a Ca2+ sensor for rapid exocytosis. We report that synaptotagmin is "tuned" to sense Ca2+ concentrations that trigger neuronal exocytosis. The speed of response is unique to synaptotagmin I and readily satisfies the kinetic constraints of synaptic vesicle membrane fusion. We further demonstrate that Ca2+ triggers penetration of synaptotagmin into membranes and simultaneously drives assembly of synaptotagmin onto the base of the ternary SNARE (soluble N-ethylmaleimide-sensitive fusion protein [NSF] attachment receptor) complex, near the transmembrane anchor of syntaxin. These data support a molecular model in which synaptotagmin triggers exocytosis through its interactions with membranes and the SNARE complex.
doi_str_mv 10.1016/S0896-6273(00)80850-8
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subjects Animals
Calcium - physiology
Calcium-Binding Proteins
Kinetics
Membrane Fusion - physiology
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membrane Proteins - metabolism
Membranes - metabolism
Nerve Tissue Proteins - chemistry
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Rats
Repetitive Sequences, Nucleic Acid
Sequence Homology
SNARE Proteins
Synaptic Vesicles - metabolism
Synaptotagmin I
Synaptotagmins
Vesicular Transport Proteins
title Kinetics of synaptotagmin responses to Ca2+ and assembly with the core SNARE complex onto membranes
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