Synaptotagmin I functions as a calcium regulator of release probability

被引:750
作者
Fernández-Chacón, R
Königstorfer, A
Gerber, SH
García, J
Matos, MF
Stevens, CF
Brose, N
Rizo, J
Rosenmund, C
Südhof, TC
机构
[1] Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dept Mol Genet, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA
[3] Max Planck Inst Expt Med, D-37070 Gottingen, Germany
[4] Max Planck Inst Biophys Chem, D-37070 Gottingen, Germany
[5] Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA
[6] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA
[7] Salk Inst Biol Studies, La Jolla, CA 92037 USA
[8] Howard Hughes Med Inst, La Jolla, CA 92037 USA
关键词
D O I
10.1038/35065004
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In all synapses, Ca2+ triggers neurotransmitter release to initiate signal transmission. Ca2+ presumably acts by activating synaptic Ca2+ sensors, but the nature of these sensors-which are the gatekeepers to neurotransmission-remains unclear. One of the candidate Ca2+ sensors in release is the synaptic Ca2+-binding protein synaptotagmin I. Here we have studied a point mutation in synaptotagmin I that causes a twofold decrease in overall Ca2+ affinity without inducing structural or conformational changes. When introduced by homologous recombination into the endogenous synaptotagmin I gene in mice, this point mutation decreases the Ca2+ sensitivity of neurotransmitter release twofold, but does not alter spontaneous release or the size of the readily releasable pool of neurotransmitters. Therefore, Ca2+ binding to synaptotagmin I participates in triggering neurotransmitter release at the synapse.
引用
收藏
页码:41 / 49
页数:9
相关论文
共 49 条
[1]   Munc13-1 is essential for fusion competence of glutamatergic synoptic vesicles [J].
Augustin, I ;
Rosenmund, C ;
Südhof, TC ;
Brose, N .
NATURE, 1999, 400 (6743) :457-461
[2]   EXCITATORY AND INHIBITORY AUTAPTIC CURRENTS IN ISOLATED HIPPOCAMPAL-NEURONS MAINTAINED IN CELL-CULTURE [J].
BEKKERS, JM ;
STEVENS, CF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) :7834-7838
[3]   The concept of a calcium sensor in transmitter release [J].
Bennett, MR .
PROGRESS IN NEUROBIOLOGY, 1999, 59 (03) :243-277
[4]  
BLASI J, 1993, EMBO J, V12, P4821, DOI 10.1002/j.1460-2075.1993.tb06171.x
[5]   Calcium sensitivity of glutamate release in a calyx-type terminal [J].
Bollmann, JH ;
Sakmann, B ;
Gerard, J ;
Borst, G .
SCIENCE, 2000, 289 (5481) :953-957
[6]   Calcium influx and transmitter release in a fast CNS synapse [J].
Borst, JGG ;
Sakmann, B .
NATURE, 1996, 383 (6599) :431-434
[7]   SYNAPTOTAGMIN - A CALCIUM SENSOR ON THE SYNAPTIC VESICLE SURFACE [J].
BROSE, N ;
PETRENKO, AG ;
SUDHOF, TC ;
JAHN, R .
SCIENCE, 1992, 256 (5059) :1021-1025
[8]   Calcium sensors in regulated exocytosis [J].
Burgoyne, RD ;
Morgan, A .
CELL CALCIUM, 1998, 24 (5-6) :367-376
[9]   Interactions of presynaptic Ca2+ channels and snare proteins in neurotransmitter release [J].
Catterall, WA .
MOLECULAR AND FUNCTIONAL DIVERSITY OF ION CHANNELS AND RECEPTORS, 1999, 868 :144-159
[10]   A novel function for the second C2 domain of synaptotagmin - Ca2+-triggered dimerization [J].
Chapman, ER ;
An, S ;
Edwardson, JM ;
Jahn, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (10) :5844-5849