ABSENCE OF SYNAPTOTAGMIN DISRUPTS EXCITATION-SECRETION COUPLING DURING SYNAPTIC TRANSMISSION
ABSENCE OF SYNAPTOTAGMIN DISRUPTS EXCITATION-SECRETION COUPLING DURING SYNAPTIC TRANSMISSION
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DOI：
10.1073/pnas.91.22.10727
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发表时间：
1994-10-25
影响因子：
11.1
通讯作者：
SCHWARZ, TL
中科院分区：
文献类型：
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作者：
BROADIE, K;BELLEN, HJ;SCHWARZ, TL
Synaptotagmin是一种整合的突触囊泡蛋白，被认为参与突触传递过程中的Ca 2+依赖性胞吐。已经在果蝇中进行了突触结合蛋白的突变，并且已经在神经肌肉突触中测定了该蛋白的体内功能。在缺乏突触结合蛋白的情况下，突触传递显著受损，但不被消除。在无效突变体中，诱发的囊泡释放减少了10倍。此外，兴奋-分泌偶联的保真度受损，使得给定的刺激产生更可变的分泌量。然而，这种残余的诱发释放显示出类似于正常释放的Ca 2+依赖性，这表明突触结合蛋白不是Ca 2+传感器，或者存在第二个独立的Ca 2+传感器。虽然诱发传输被抑制，自发囊泡融合率增加了5倍。我们的结论是，synaptotagmin是不是一个绝对必要的组成部分，在突触传递的钙依赖性分泌途径，但必须为正常水平的传输。我们的数据支持一个模型，其中synaptotagmin的功能作为一个负调节器的自发囊泡融合，并采取行动，以提高效率的兴奋分泌耦合在突触传递。
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.