Universität zu Köln

Miller, Sharon E., Sahlender, Daniela A., Graham, Stephen C., Hoening, Stefan, Robinson, Margaret S., Peden, Andrew A. and Owen, David J. (2011). The Molecular Basis for the Endocytosis of Small R-SNAREs by the Clathrin Adaptor CALM. Cell, 147 (5). S. 1118 - 1132. CAMBRIDGE: CELL PRESS. ISSN 0092-8674

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Miller, Sharon E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahlender, Daniela A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Graham, Stephen C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoening, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, Margaret S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peden, Andrew A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Owen, David J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-485153
DOI:	10.1016/j.cell.2011.10.038
Journal or Publication Title:	Cell
Volume:	147
Number:	5
Page Range:	S. 1118 - 1132
Date:	2011
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	0092-8674
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANS-GOLGI NETWORK; COATED VESICLES; ALZHEIMERS-DISEASE; SYNAPTIC VESICLES; CRYSTAL-STRUCTURE; COMPLEX-FORMATION; EARLY ENDOSOMES; FUSION PROTEIN; TRAFFICKING; AP180 Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48515