RGD Reference Report - SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses. - Rat Genome Database

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SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses.

Authors: Koo, Seong Joo  Markovic, Stefan  Puchkov, Dmytro  Mahrenholz, Carsten C  Beceren-Braun, Figen  Maritzen, Tanja  Dernedde, Jens  Volkmer, Rudolf  Oschkinat, Hartmut  Haucke, Volker 
Citation: Koo SJ, etal., Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13540-5. doi: 10.1073/pnas.1107067108. Epub 2011 Aug 1.
RGD ID: 13506237
Pubmed: PMID:21808019   (View Abstract at PubMed)
PMCID: PMC3158172   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1107067108   (Journal Full-text)

Neurotransmission depends on the exo-endocytosis of synaptic vesicles at active zones. Synaptobrevin 2 [also known as vesicle-associated membrane protein 2 (VAMP2)], the most abundant synaptic vesicle protein and a major soluble NSF attachment protein receptor (SNARE) component, is required for fast calcium-triggered synaptic vesicle fusion. In contrast to the extensive knowledge about the mechanism of SNARE-mediated exocytosis, little is known about the endocytic sorting of synaptobrevin 2. Here we show that synaptobrevin 2 sorting involves determinants within its SNARE motif that are recognized by the ANTH domains of the endocytic adaptors AP180 and clathrin assembly lymphoid myeloid leukemia (CALM). Depletion of CALM or AP180 causes selective surface accumulation of synaptobrevin 2 but not vGLUT1 at the neuronal surface. Endocytic sorting of synaptobrevin 2 is mediated by direct interaction of the ANTH domain of the related endocytic adaptors CALM and AP180 with the N-terminal half of the SNARE motif centered around M46, as evidenced by NMR spectroscopy analysis and site-directed mutagenesis. Our data unravel a unique mechanism of SNARE motif-dependent endocytic sorting and identify the ANTH domain proteins AP180 and CALM as cargo-specific adaptors for synaptobrevin endocytosis. Defective SNARE endocytosis may also underlie the association of CALM and AP180 with neurodevelopmental and cognitive defects or neurodegenerative disorders.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PicalmRatpositive regulation of synaptic vesicle endocytosis  IMP  RGD 
Snap91Ratpositive regulation of synaptic vesicle endocytosis  IMP  RGD 
Vamp2Ratregulation of synaptic vesicle recycling  IMP  RGD 
PicalmRatsynaptic vesicle endocytosis involved_inIMP PMID:21808019SynGO 
PicalmRatsynaptic vesicle endocytosis involved_inIDA PMID:21808019SynGO 
Snap91Ratsynaptic vesicle endocytosis involved_inIMP PMID:21808019SynGO 
Snap91Ratsynaptic vesicle endocytosis involved_inIDA PMID:21808019SynGO 

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Vamp2Ratprotein binding  IPIPicalm (Rattus norvegicus) RGD 
Vamp2Ratprotein binding  IPISnap91 (Rattus norvegicus) RGD 
PicalmRatSNARE binding  IPIVamp2 (Rattus norvegicus) RGD 
Snap91RatSNARE binding  IPIVamp2 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Picalm  (phosphatidylinositol binding clathrin assembly protein)
Snap91  (synaptosome associated protein 91)
Vamp2  (vesicle-associated membrane protein 2)


Additional Information