V-ATP酶V0亚基a1是果蝇突触小泡胞吐作用后期步骤所必需的。
The v-ATPase V0 subunit a1 is required for a late step in synaptic vesicle exocytosis in Drosophila.
作者信息
Hiesinger P Robin, Fayyazuddin Amir, Mehta Sunil Q, Rosenmund Tanja, Schulze Karen L, Zhai R Grace, Verstreken Patrik, Cao Yu, Zhou Yi, Kunz Jeannette, Bellen Hugo J
机构信息
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.
出版信息
Cell. 2005 May 20;121(4):607-620. doi: 10.1016/j.cell.2005.03.012.
The V(0) complex forms the proteolipid pore of an ATPase that acidifies vesicles. In addition, an independent function in membrane fusion has been proposed largely based on yeast vacuolar fusion experiments. We have isolated mutations in the largest V(0) component vha100-1 in flies in an unbiased genetic screen for synaptic malfunction. The protein is only required in neurons, colocalizes with markers for synaptic vesicles as well as active zones, and interacts with t-SNAREs. Loss of vha100-1 leads to vesicle accumulation in synaptic terminals, suggesting a deficit in release. The amplitude of spontaneous release events and release with hypertonic stimulation indicate normal levels of neurotransmitter loading, yet mutant embryos display severe defects in evoked synaptic transmission and FM1-43 uptake. Our data suggest that Vha100-1 functions downstream of SNAREs in synaptic vesicle fusion.
V(0)复合体形成了一种使囊泡酸化的ATP酶的蛋白脂质孔道。此外，基于酵母液泡融合实验，人们很大程度上提出了其在膜融合中的独立功能。我们在一项针对突触功能障碍的无偏向性遗传筛选中，分离出了果蝇中最大的V(0)组分vha100-1的突变。该蛋白仅在神经元中需要，与突触小泡以及活性区的标记物共定位，并与t-SNARE相互作用。vha100-1的缺失导致突触末端囊泡积累，提示释放存在缺陷。自发释放事件的幅度以及高渗刺激下的释放表明神经递质装载水平正常，但突变胚胎在诱发的突触传递和FM1-43摄取方面表现出严重缺陷。我们的数据表明，Vha100-1在突触小泡融合中在SNAREs下游发挥作用。
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