Chen Li, Lau Martin S Y, Banfield David K
Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.
Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China
Mol Biol Cell. 2016 Sep 1;27(17):2633-41. doi: 10.1091/mbc.E16-05-0277. Epub 2016 Jul 6.
The formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes between opposing membranes is an essential prerequisite for fusion between vesicles and their target compartments. The composition and length of a SNARE's transmembrane domain (TMD) is also an indicator for their steady-state distribution in cells. The evolutionary conservation of the SNARE TMD, together with the strict requirement of this feature for membrane fusion in biochemical studies, implies that the TMD represents an essential protein module. Paradoxically, we find that for several essential ER- and Golgi-localized SNAREs, a TMD is unnecessary. Moreover, in the absence of a covalent membrane tether, such SNAREs can still support ER-Golgi vesicle transport and recapitulate established genetic interactions. Transport anomalies appear to be restricted to retrograde trafficking, but these defects are overcome by the attachment of a C-terminal lipid anchor to the SNARE. We conclude that the TMD functions principally to support the recycling of Qb-, Qc-, and R-SNAREs and, in so doing, retrograde transport.
相对膜之间可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）复合物的形成是囊泡与其靶区室融合的必要前提。SNARE跨膜结构域（TMD）的组成和长度也是其在细胞中稳态分布的一个指标。SNARE TMD的进化保守性，以及生化研究中该特征对膜融合的严格要求，意味着TMD代表一个必需的蛋白质模块。矛盾的是，我们发现对于几种定位于内质网和高尔基体的必需SNARE来说，TMD并非必需。此外，在没有共价膜系链的情况下，此类SNARE仍能支持内质网 - 高尔基体囊泡运输并重现已确立的遗传相互作用。运输异常似乎仅限于逆行运输，但通过将C末端脂质锚定连接到SNARE上可克服这些缺陷。我们得出结论，TMD的主要功能是支持Qb - 、Qc - 和R - SNARE的循环利用，并由此支持逆行运输。
