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: (View Article at PubMed) PMID:21808019
DOI: Full-text: DOI:10.1073/pnas.1107067108

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.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

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


Additional Information