title: Vesicular glutamate transporter 1 orchestrates recruitment of other synaptic vesicle cargo proteins during synaptic vesicle recycling.
abstract: A long standing question in synaptic physiology is how neurotransmitter-filled vesicles are rebuilt after exocytosis. Among the first steps in this process is the endocytic retrieval of the transmembrane proteins that are enriched in synaptic vesicles (SVs). At least six types of transmembrane proteins must be recovered, but the rules for how this multiple cargo selection is accomplished are poorly understood. Among these SV cargos is the vesicular glutamate transporter (vGlut). We show here that vGlut1 has a strong influence on the kinetics of retrieval of half of the known SV cargos and that specifically impairing the endocytosis of vGlut1 in turn slows down other SV cargos, demonstrating that cargo retrieval is a collective cargo-driven process. Finally, we demonstrate that different cargos can be retrieved in the same synapse with different kinetics, suggesting that additional post-endocytic sorting steps likely occur in the nerve terminal.
authors.affiliation: From the Department of Biochemistry, Weill Cornell Medical College, New York, New York 10021.
authors.forename: Ping-Yue
authors.initials: PY
authors.lastname: Pan
authors.affiliation: From the Department of Biochemistry, Weill Cornell Medical College, New York, New York 10021.
authors.forename: Julia
authors.initials: J
authors.lastname: Marrs
authors.affiliation: From the Department of Biochemistry, Weill Cornell Medical College, New York, New York 10021 taryan@med.cornell.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Ryan
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000378:metabolism*; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*
chemical_list: C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1
keywords: endocytosis; gene silencing; glutamate transporter; membrane recycling; microscopic imaging; neuron; protein sorting; synapse; vGlut; vesicles