The Molecular Basis for the Endocytosis of Small R-SNAREs by the Clathrin Adaptor CALM

被引：163

作者：

Miller, Sharon E. ^{[1
,2
]}

Sahlender, Daniela A. ^{[1
,2
]}

Graham, Stephen C. ^{[1
,2
]}

Hoening, Stefan ^{[3
,4
]}

Robinson, Margaret S. ^{[1
,2
]}

Peden, Andrew A. ^{[1
,2
]}

Owen, David J. ^{[1
,2
]}

机构：

[1] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England

[2] Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 0XY, England

[3] Univ Cologne, Inst Biochem 1, D-50931 Cologne, Germany

[4] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany

来源：

CELL | 2011年 / 147卷 / 05期

基金：

英国惠康基金;

关键词：

TRANS-GOLGI NETWORK; COATED VESICLES; ALZHEIMERS-DISEASE; SYNAPTIC VESICLES; CRYSTAL-STRUCTURE; COMPLEX-FORMATION; EARLY ENDOSOMES; FUSION PROTEIN; TRAFFICKING; AP180;

D O I：

10.1016/j.cell.2011.10.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

SNAREs provide a large part of the specificity and energy needed for membrane fusion and, to do so, must be localized to their correct membranes. Here, we show that the R-SNAREs VAMP8, VAMP3, and VAMP2, which cycle between the plasma membrane and endosomes, bind directly to the ubiquitously expressed, PtdIns4, 5P(2)-binding, endocytic clathrin adaptor CALM/PICALM. X-ray crystallography shows that the N-terminal halves of their SNARE motifs bind the CALM(ANTH) domain as helices in a manner that mimics SNARE complex formation. Mutation of residues in the CALM: SNARE interface inhibits binding in vitro and prevents R-SNARE endocytosis in vivo. Thus, CALM: R-SNARE interactions ensure that R-SNAREs, required for the fusion of endocytic clathrin-coated vesicles with endosomes and also for subsequent postendosomal trafficking, are sorted into endocytic vesicles. CALM's role in directing the endocytosis of small R-SNAREs may provide insight into the association of CALM/PICALMmutations with growth retardation, cognitive defects, and Alzheimer's disease.

引用

页码：1118 / 1131

页数：14

共 53 条

[1]

Seven novel mammalian SNARE proteins localize to distinct membrane compartments [J].