SYNAPTOTAGMIN-I - A MAJOR CA2+ SENSOR FOR TRANSMITTER RELEASE AT A CENTRAL SYNAPSE
SYNAPTOTAGMIN-I - A MAJOR CA2+ SENSOR FOR TRANSMITTER RELEASE AT A CENTRAL SYNAPSE
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DOI：
10.1016/0092-8674(94)90556-8
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发表时间：
1994-11-18
期刊：
影响因子：
64.5
通讯作者：
SUDHOF, TC
中科院分区：
文献类型：
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作者：
GEPPERT, M;GODA, Y;SUDHOF, TC
携带突触素I基因突变的小鼠是通过同源重组产生的。突变小鼠的表型正常为杂合子，但出生后48小时内死亡为纯合子。对纯合子突变小鼠海马神经元培养的研究表明，突触传递严重受损。钙依赖神经递质释放的同步、快速成分减少，而非同步释放过程，包括自发突触活动(微小的兴奋性突触后电流频率)和由高渗溶液或α-乳杆菌毒素触发的释放，不受影响。我们的研究结果表明，突触素I功能是钙离子触发神经递质同步释放所必需的，但对异步或非钙非依赖性神经递质释放不是必需的。我们认为，突触素I是主要的低亲和力钙离子感受器，介导钙离子对海马神经元同步神经递质释放的调节。
Mice carrying a mutation in the synaptotagmin I gene were generated by homologous recombination. Mutant mice are phenotypically normal as heterozygotes, but die within 48 hr after birth as homozygotes. Studies of hippocampal neurons cultured from homozygous mutant mice reveal that synaptic transmission is severely impaired. The synchronous, fast component of Ca2+-dependent neurotransmitter release is decreased, whereas asynchronous release processes, including spontaneous synaptic activity (miniature excitatory postsynaptic current frequency) and release triggered by hypertonic solution or alpha-latrotoxin, are unaffected. Our findings demonstrate that synaptotagmin I function is required for Ca2+ triggering of synchronous neurotransmitter release, but is not essential for asynchronous or Ca2+-independent release. We propose that synaptotagmin I is the major low affinity Ca2+ sensor mediating Ca2+ regulation of synchronous neurotransmitter release in hippocampal neurons.