A Presynaptic Role for the Cytomatrix Protein GIT in Synaptic Vesicle Recycling

• DOI: 10.1016/j.celrep.2014.04.051
• Publication Date: 2014-05-29T16:21:50Z
• Authors: Jasmin Podufall; Rui Tian; Elena Knoche; Dmytro Puchkov; Alexander M. Walter; Stefanie Rosa; Christine Quentin; Anela Vukoja; Nadja Jung; Andre Lampe; Carolin Wichmann; Mathias Böhme; Harald Depner; Yong Q. Zhang; Jan Schmoranzer; Stephan J. Sigrist; Volker Haucke
• Keywords: 0301 basic medicine; 570; QH301-705.5; GTPase-Activating Proteins; Presynaptic Terminals; Nerve Tissue Proteins; Endocytosis; Exocytosis; 12. Responsible consumption; Synaptotagmins; 03 medical and health sciences; GTP-Binding Protein Regulators; Animals; Drosophila Proteins; Drosophila; Synaptic Vesicles; Biology (General); Carrier Proteins; Protein Binding

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.