| First Author | Miller SE | Year | 2011 |
| Journal | Cell | Volume | 147 |
| Issue | 5 | Pages | 1118-31 |
| PubMed ID | 22118466 | Mgi Jnum | J:182470 |
| Mgi Id | MGI:5315673 | Doi | 10.1016/j.cell.2011.10.038 |
| Citation | Miller SE, et al. (2011) The molecular basis for the endocytosis of small R-SNAREs by the clathrin adaptor CALM. Cell 147(5):1118-31 |
| abstractText | 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. |
