Members of the synaptobrevin/vesicle-associated membrane protein (VAMP) family in Drosophila are functionally interchangeable in vivo for neurotransmitter release and cell viability
Members of the synaptobrevin/vesicle-associated membrane protein (VAMP) family in Drosophila are functionally interchangeable in vivo for neurotransmitter release and cell viability
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DOI：
10.1073/pnas.202335999
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发表时间：
2002-10-15
影响因子：
11.1
通讯作者：
Schwarz, TL
中科院分区：
文献类型：
--
作者：
Bhattacharya, S;Stewart, BA;Schwarz, TL
突触小泡蛋白或VAMPS是囊泡相关的膜蛋白，通常称为V-SNARES，其对于囊泡在质膜上的运输和融合是重要的。果蝇有两个典型的基因家族成员：小突触泡蛋白（syb）和神经元小突触泡蛋白（n-syb）。突变的表型和基因表达模式表明，n-Syb是唯一的神经元和突触囊泡分泌所需的，而Syb是无处不在的，如这里所示，细胞活力所必需的。当眼睛的前体细胞是syb（-）的纯合子时，眼睛就不能发育了。相比之下，n-syb（-）眼克隆发育正常，但未能激活下游神经元。为了确定这两种蛋白质是否在结构上专门化以实现这些不同的体内功能，我们在没有其他基因的情况下驱动每个基因的表达以寻找表型拯救。我们发现在眼睛发育过程中n-syb的表达可以挽救syb突变的细胞致死性，大鼠VAMP 2和cellubrevin也可以。通过视网膜电图和神经肌肉接头处兴奋性连接电流的记录，syb的表达可以恢复n-syb突变体的突触传递。因此，我们发现，Syb，这通常是不参与突触功能，可以介导的Ca 2+触发的突触活动，并没有特殊的专门化的v-SNARE需要区分突触胞吐从其他形式。
Synaptobrevins or VAMPS are vesicle-associated membrane proteins, often called v-SNARES, that are important for vesicle transport and fusion at the plasma membrane. Drosophila has two characterized members of this gene family: synaptobrevin (syb) and neuronal synaptobrevin (n-syb). Mutant phenotypes and gene-expression patterns indicate that n-Syb is exclusively neuronal and required only for synaptic vesicle secretion, whereas Syb is ubiquitous and, as shown here, essential for cell viability. When the eye precursor cells were made homozygous for syb(-), the eye failed to develop. In contrast, n-syb(-) eye clones developed appropriately but failed to activate downstream neurons. To determine whether the two proteins are structurally specialized to accomplish these distinct in vivo functions, we have driven the expression of each gene in the absence of the other to look for phenotypic rescue. We find that expression of n-syb during eye development can rescue the cell lethality of the syb mutations, as can rat VAMP2 and cellubrevin. Expression of syb can restore synaptic transmission to n-syb mutants as assayed both by electroretinogram and recordings of excitatory junctional currents at the neuromuscular junction. Therefore, we find that Syb, which usually is not involved in synaptic function, can mediate Ca2+-triggered synaptic activity and that no particular specialization of the v-SNARE is required to differentiate synaptic exocytosis from other forms.