Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, UK.
Traffic. 2010 May;11(5):688-705. doi: 10.1111/j.1600-0854.2010.01049.x.
Membrane fusion is dependent on the function of SNAREs and their alpha-helical SNARE motifs that form SNARE complexes. The Habc domains at the N-termini of some SNAREs can interact with their associated SNARE motif, Sec1/Munc18 (SM) proteins, tethering proteins or adaptor proteins, suggesting that they play an important regulatory function. We screened for proteins that interact with the Habc domain of Syntaxin 6, and isolated an uncharacterized 164-kDa protein that we named SHIP164. SHIP164 is part of a large (approximately 700 kDa) complex, and interacts with components of the Golgi-associated retrograde protein (GARP) tethering complex. Depletion of GARP subunits or overexpression of Syntaxin 6 results in a redistribution of soluble SHIP164 to endosomal structures. Co-overexpression of Syntaxin 6 and SHIP164 produced excessive tubulation of endosomes, and perturbed the transport of cation-independent mannose-6-phosphate receptor (CI-MPR) and transferrin receptor. Thus,we propose that SHIP164 functions in trafficking through the early/recycling endosomal system.
膜融合依赖于 SNAREs 的功能及其形成 SNARE 复合物的α-螺旋 SNARE 基序。一些 SNAREs 的 N 端 Habc 结构域可以与它们相关的 SNARE 基序、Sec1/Munc18（SM）蛋白、连接蛋白或衔接蛋白相互作用，这表明它们发挥着重要的调节作用。我们筛选了与突触融合蛋白 6 的 Habc 结构域相互作用的蛋白质，并分离到一种未被描述的 164kDa 蛋白质，我们将其命名为 SHIP164。SHIP164 是一个大的（约 700kDa）复合物的一部分，并与高尔基体相关逆行蛋白（GARP）连接复合物的成分相互作用。GARP 亚基的耗竭或突触融合蛋白 6 的过表达导致可溶性 SHIP164 重新分布到内体结构中。突触融合蛋白 6 和 SHIP164 的共表达导致内体过度管腔化，并干扰阳离子非依赖性甘露糖-6-磷酸受体（CI-MPR）和转铁蛋白受体的运输。因此，我们提出 SHIP164 在内体再循环系统的运输中发挥作用。
