INTERACTION OF RAB3A W/ SYNAPTIC VESICLES

我们之前已经证明了钙和钙结合蛋白， 钙调蛋白，可以共同作用取代低分子质量 猕猴大脑前额叶皮质突触小泡中的GTPase、Rab 3A 膜。这一发现具有潜在的意义，因为突触 囊泡结合的Rab 3A被认为影响钙触发的 轴突终末释放神经递质。事实是， 钙调素能取代突触囊泡膜上的Rab 3A 体外实验增加了钙/钙调蛋白可能具有类似的 体内效应。在过去的一年里，我们在 一项与洛桑大学研究人员的合作研究 在瑞士。研究结果表明，一种突变形式的 不能结合钙/钙调素的RAB3对刺激的钙通道无影响 胞吐事件。这表明Rab3与Rab3的络合物 正常情况下响应升高而产生的CA2/钙调蛋白 钙离子浓度可减少兴奋性事件的发生 对分泌性刺激的反应。资助美国国立卫生研究院拨款 RR00166和霍华德·休斯医学院。

We showed previously that Ca2+ and the Ca2+-binding protein, calmodulin, can act together to displace the low molecular mass GTPase, Rab 3A from macaque brain prefrontal cortex synaptic vesicle membranes. This finding was of potential interest because synaptic vesicle-bound Rab 3A is thought to influence the Ca2+-triggered release of neurotransmitters from axonal termini. The fact that Ca2+/calmodulin can displace Rab 3A from synaptic vesicle membranes in vitro raises the possibility that Ca2+/calmodulin may have a similar effect in vivo. During the past year we explored this possibility in a collaborative study with investigators at the University of Lausanne in Switzerland. The results of the study showed that a mutant form of Rab 3 that cannot bind Ca2+/calmodulin has no effect on stimulated exocytotic events. This suggests that the complex of Rab 3 with Ca2+/calmodulin that is normally generated in response to elevated concentrations of Ca2+ may reduce the numbe r of exocy totic events that occur in response to secretory stimuli. FUNDING NIH grant RR00166 and the Howard Hughes Medical Institute.