Abstract
SummarySNAREs 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, PtdIns4,5P2-binding, endocytic clathrin adaptor CALM/PICALM. X-ray crystallography shows that the N-terminal halves of their SNARE motifs bind the CALMANTH 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.
Highlights
SNAREs (Soluble NSF Attachment Protein REceptors) are small membrane-anchored proteins that lie at the heart of the vesicle:organelle and organelle:organelle membrane fusion machinery, providing much of the energy and specificity required for membrane fusion (Hong, 2005; Jahn and Scheller, 2006; Sutton et al, 1998)
We show that the R-SNAREs VAMP8, VAMP3, and VAMP2, which cycle between the plasma membrane and endosomes, bind directly to the ubiquitously expressed, PtdIns4,5P2-binding, endocytic clathrin adaptor CALM/PICALM
X-ray crystallography shows that the N-terminal halves of their SNARE motifs bind the CALMANTH domain as helices in a manner that mimics SNARE complex formation
Summary
SNAREs (Soluble NSF Attachment Protein REceptors) are small membrane-anchored proteins that lie at the heart of the vesicle:organelle and organelle:organelle membrane fusion machinery, providing much of the energy and specificity required for membrane fusion (Hong, 2005; Jahn and Scheller, 2006; Sutton et al, 1998). SNARE complexes are formed when four SNARE motifs come together as a tetrameric coiled-coil (Sutton et al, 1998). Three of these SNARE motifs are associated with one membrane and derive from the so-called Q-SNAREs, while the other SNARE motif is provided by an R-SNARE that resides in the membrane that will fuse with the first membrane (Fasshauer et al, 1998). SNAREs must be transported to a given organelle membrane so that they can subsequently be sorted into transport vesicles and tubules leaving that membrane since this enables these transport vesicles/tubules to fuse, with their desired target membrane, into which the correct cognate SNAREs must have already been placed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
