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J Cell Biol. 2007 Dec 31;179(7):1497-510. doi: 10.1083/jcb.200708107.

Molecular basis of synaptic vesicle cargo recognition by the endocytic sorting adaptor stonin 2.

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1
Department of Membrane Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

Abstract

Synaptic transmission depends on clathrin-mediated recycling of synaptic vesicles (SVs). How select SV proteins are targeted for internalization has remained elusive. Stonins are evolutionarily conserved adaptors dedicated to endocytic sorting of the SV protein synaptotagmin. Our data identify the molecular determinants for recognition of synaptotagmin by stonin 2 or its Caenorhabditis elegans orthologue UNC-41B. The interaction involves the direct association of clusters of basic residues on the surface of the cytoplasmic domain of synaptotagmin 1 and a beta strand within the mu-homology domain of stonin 2. Mutation of K783, Y784, and E785 to alanine within this stonin 2 beta strand results in failure of the mutant stonin protein to associate with synaptotagmin, to accumulate at synapses, and to facilitate synaptotagmin internalization. Synaptotagmin-binding-defective UNC-41B is unable to rescue paralysis in C. elegans stonin mutant animals, suggesting that the mechanism of stonin-mediated SV cargo recognition is conserved from worms to mammals.

PMID:
18166656
PMCID:
PMC2373488
DOI:
10.1083/jcb.200708107
[Indexed for MEDLINE]
Free PMC Article
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