Sec17 (α-SNAP) and Sec18 (NSF) restrict membrane fusion to R-SNAREs, Q-SNAREs, and SM proteins from identical compartments.
Sec17 (α-SNAP) and Sec18 (NSF) restrict membrane fusion to R-SNAREs, Q-SNAREs, and SM proteins from identical compartments.
复制标题
Sec17 (α-SNAP) 和 Sec18 (NSF) 将膜融合限制为来自相同隔室的 R-SNARE、Q-SNARE 和 SM 蛋白。
DOI：
10.1073/pnas.1913985116
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发表时间：
2019
影响因子：
11.1
通讯作者：
Wickner,William
中科院分区：
文献类型：
--
作者：
Jun,Youngsoo;Wickner,William
每个细胞器的膜融合需要保守的蛋白质：Rab-GTP酶、效应子束缚复合物、Sec1/Munc18 (SM)家族SNARE伴侣、R、Qa、Qb和Qc家族的SNARE，以及Sec17/α-SNAP和ATP依赖性Sec18/NSF SNARE伴侣系统。细胞器特异性融合对于准确的蛋白质区室至关重要，但其基础一直难以捉摸。 Rab 家族 GTPases、SM 蛋白以及 R-和 Q-SNARE 可能有助于这种特异性。我们现在报道，仅由 SNARE 支持的融合在细胞器特性和 SM 家族蛋白或复合物的刺激方面既低效又混杂。仅 SNARE 融合被拆卸伴侣 Sec17 和 Sec18 废除。 Sec17 和 Sec18 存在下的有效融合需要 R-SNARE、Q-SNARE 和 SM 蛋白或复合物的细胞器身份之间的三方匹配。 Sec17和Sec18的作用并不是简单的负调节，而是负调节。它们刺激与液泡 SNARE 及其 SM 蛋白复合物 HOPS 或内质网/顺式高尔基体 SNARE 及其 SM 蛋白 Sly1 的融合。每个细胞器的融合复合体由其自身功能匹配的片段组装而成，以接合 Sec17/Sec18 来刺激融合而不是抑制。
Membrane fusion at each organelle requires conserved proteins: Rab-GTPases, effector tethering complexes, Sec1/Munc18 (SM)-family SNARE chaperones, SNAREs of the R, Qa, Qb, and Qc families, and the Sec17/α-SNAP and ATP-dependent Sec18/NSF SNARE chaperone system. The basis of organelle-specific fusion, which is essential for accurate protein compartmentation, has been elusive. Rab family GTPases, SM proteins, and R- and Q-SNAREs may contribute to this specificity. We now report that the fusion supported by SNAREs alone is both inefficient and promiscuous with respect to organelle identity and to stimulation by SM family proteins or complexes. SNARE-only fusion is abolished by the disassembly chaperones Sec17 and Sec18. Efficient fusion in the presence of Sec17 and Sec18 requires a tripartite match between the organellar identities of the R-SNARE, the Q-SNAREs, and the SM protein or complex. The functions of Sec17 and Sec18 are not simply negative regulation; they stimulate fusion with either vacuolar SNAREs and their SM protein complex HOPS or endoplasmic reticulum/cis-Golgi SNAREs and their SM protein Sly1. The fusion complex of each organelle is assembled from its own functionally matching pieces to engage Sec17/Sec18 for fusion stimulation rather than inhibition.