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Cited by 192Cellular transport and secretionAutophagy in Disease and TherapyMicrotubule and mitosis dynamics

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

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Miller, Sharon E., Sahlender, Daniela A., Graham, Stephen C., Höning, Stefan, Robinson, Margaret S., Peden, Andrew A., Owen, David J.·2011·Cell
DOI 10.1016/j.cell.2011.10.038PMC PMC3267021
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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/PICALM mutations with growth retardation, cognitive defects, and Alzheimer's disease.

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  • PICALM controls receptor internalization and subsequent intracellular trafficking via R-SNARE-mediated fusion of clathrin-coated vesicles with endosomes.

    “PICALM controls receptor internalization and subsequent intracellular trafficking (683), via R-SNARE-mediated fusion of clathrin-coated vesicles with endosomes (411).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [411]

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References 70 · Cited by 192

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Authors
Miller, S. E., Sahlender, D. A., Graham, S. C., Höning, S., Robinson, M. S., Peden, A. A., & Owen, D. J.
Affiliations
  • University of Cambridge (GB)
  • University of Cologne (DE)
Corresponding author
  • Peden, Andrew A.
  • Owen, David J.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2011-11
Volume
147
Issue
5
Pages
1118-1131
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2011.10.038
PMC
PMC3267021
OpenAlex
W2153685501
Cited by
192
References
70
Citations by year
2026: 5 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 14 · 2021: 16 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 15 · 2016: 13 · 2015: 17 · 2014: 21 · 2013: 18 · 2012: 15
FWCI
8.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
Funders
  • Wellcome Trust (090909)
  • Diamond Light Source
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
R-SNARE, clathrin adaptor proteins, endocytosis, VAMP8, VAMP3, VAMP2, SNARE motif, membrane fusion, endosomal trafficking, clathrin-coated vesicles, Alzheimer's disease, growth retardation, cognitive defects
MeSH terms
Animals, Cell Membrane, Endocytosis, HeLa Cells, Humans, Models, Molecular, Crystallography, X-Ray, Transport Vesicles, Monomeric Clathrin Assembly Proteins, SNARE Proteins, R-SNARE Proteins, Mice, Rats

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