title: A presynaptic role for the cytomatrix protein GIT in synaptic vesicle recycling.
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.
authors.affiliation: Leibniz 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.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Podufall
authors.affiliation: Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.affiliation: NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Virchowweg 6, 10117 Berlin, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Knoche
authors.affiliation: Leibniz 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.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Puchkov
authors.affiliation: Leibniz 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.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Walter
authors.affiliation: Leibniz Institute for Molecular Pharmacology, Robert Rössle Strasse 10, 13125 Berlin, Germany; Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rosa
authors.affiliation: Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Quentin
authors.affiliation: Leibniz 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.
authors.forename: Anela
authors.initials: A
authors.lastname: Vukoja
authors.affiliation: Membrane Biochemistry, Institute of Chemistry & Biochemistry, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Jung
authors.affiliation: Leibniz 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.
authors.forename: Andre
authors.initials: A
authors.lastname: Lampe
authors.affiliation: Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Wichmann
authors.affiliation: Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Böhme
authors.affiliation: Genetics, Institute for Biology, Freie Universität Berlin, Takustraße 6, 14195 Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Depner
authors.affiliation: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Leibniz 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Schmoranzer
authors.affiliation: Genetics, 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.
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
authors.affiliation: Leibniz 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.
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D005089:Exocytosis; D020555:GTP-Binding Protein Regulators / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D011485:Protein Binding; D013572:Synaptic Vesicles / Q000378:metabolism*; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D020555:GTP-Binding Protein Regulators; D020690:GTPase-Activating Proteins; C534509:Git protein, Drosophila; D009419:Nerve Tissue Proteins; C420114:stnB protein, Drosophila; D050857:Synaptotagmins