An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming
An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming
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DOI：
10.1038/35085583
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发表时间：
2001-07-19
期刊：
影响因子：
64.8
通讯作者：
Jorgensen, EM
中科院分区：
文献类型：
--
作者：
Richmond, JE;Weimer, RM;Jorgensen, EM
突触囊泡胞吐的引发步骤被认为需要形成SNARE复合物，其包含蛋白质小突触泡蛋白、SNAP-25和突触融合蛋白（1-3）。在溶液中，syntaxin采用默认的封闭构型，这与SNARE复合物的形成不相容（4）。具体而言，突触融合蛋白的氨基末端结合SNARE基序并阻断与其他SNARE蛋白的相互作用。突触融合蛋白的N末端也与突触前蛋白<$3 -13结合（参考文献5）。在小鼠、果蝇和秀丽隐杆线虫中的研究表明，α-13在胞吐的后对接步骤中起作用，最可能在突触囊泡引发期间起作用（6-8）。因此，与突触融合蛋白N末端结合的β-13可能促进突触融合蛋白的开放构型（9）。为了测试这个模型，我们将突变工程化到C中。elegans syntaxin导致蛋白质组成性地采用开放构型（4）。在这里，我们证明了开放形式的突触融合蛋白可以绕过突触囊泡启动的要求，为13。因此，很可能是β-13通过促进突触融合蛋白的开放构型来引发突触囊泡的融合。
The priming step of synaptic vesicle exocytosis is thought to require the formation of the SNARE complex, which comprises the proteins synaptobrevin, SNAP-25 and syntaxin(1-3). In solution syntaxin adopts a default, closed configuration that is incompatible with formation of the SNARE complex(4). Specifically, the amino terminus of syntaxin binds the SNARE motif and occludes interactions with the other SNARE proteins. The N terminus of syntaxin also binds the presynaptic protein UNC-13 (ref. 5). Studies in mouse, Drosophila and Caenorhabditis elegans suggest that UNC-13 functions at a post-docking step of exocytosis, most likely during synaptic vesicle priming(6-8). Therefore, UNC-13 binding to the N terminus of syntaxin may promote the open configuration of syntaxin(9). To test this model, we engineered mutations into C. elegans syntaxin that cause the protein to adopt the open configuration constitutively(4). Here we demonstrate that the open form of syntaxin can bypass the requirement for UNC-13 in synaptic vesicle priming. Thus, it is likely that UNC-13 primes synaptic vesicles for fusion by promoting the open configuration of syntaxin.