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Cell Rep. 2014 Jun 12;7(5):1417-25. doi: 10.1016/j.celrep.2014.04.051. Epub 2014 May 29.

A presynaptic role for the cytomatrix protein GIT in synaptic vesicle recycling.

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  • 1Leibniz Institute for Molecular Pharmacology, Robert Rössle Strasse 10, 13125 Berlin, Germany; Membrane Biochemistry, Institute of Chemistry & Biochemistry, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
  • 2Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
  • 3NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany.
  • 4Leibniz Institute for Molecular Pharmacology, Robert Rössle Strasse 10, 13125 Berlin, Germany; Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany.
  • 5Leibniz Institute for Molecular Pharmacology, Robert Rössle Strasse 10, 13125 Berlin, Germany; Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
  • 6Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
  • 7Membrane Biochemistry, Institute of Chemistry & Biochemistry, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
  • 8Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
  • 9Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany. Electronic address: stephan.sigrist@fu-berlin.de.
  • 10Leibniz Institute for Molecular Pharmacology, Robert Rössle Strasse 10, 13125 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany; Membrane Biochemistry, Institute of Chemistry & Biochemistry, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany. Electronic address: haucke@fmp-berlin.de.

Abstract

Neurotransmission involves the exo-endocytic cycling of synaptic vesicles (SVs) within nerve terminals. Exocytosis is facilitated by a cytomatrix assembled at the active zone (AZ). The precise spatial and functional relationship between exocytic fusion of SVs at AZ membranes and endocytic SV retrieval is unknown. Here, we identify the scaffold G protein coupled receptor kinase 2 interacting (GIT) protein as a component of the AZ-associated cytomatrix and as a regulator of SV endocytosis. GIT1 and its D. melanogaster ortholog, dGIT, are shown to directly associate with the endocytic adaptor stonin 2/stoned B. In Drosophila dgit mutants, stoned B and synaptotagmin levels are reduced and stoned B is partially mislocalized. Moreover, dgit mutants show morphological and functional defects in SV recycling. These data establish a presynaptic role for GIT in SV recycling and suggest a connection between the AZ cytomatrix and the endocytic machinery.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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