title: The dynamin-binding domains of Dap160/intersectin affect bulk membrane retrieval in synapses.
abstract: Dynamin-associated protein 160 kDa (Dap160)/intersectin interacts with several synaptic proteins and affects endocytosis and synapse development. The functional role of the different protein interaction domains is not well understood. Here we show that Drosophila Dap160 lacking the dynamin-binding SH3 domains does not affect the development of the neuromuscular junction but plays a key role in synaptic vesicle recycling. dap160 mutants lacking dynamin-interacting domains no longer accumulate dynamin properly at the periactive zone, and it becomes dispersed in the bouton during stimulation. This is accompanied by a reduction in uptake of the dye FM1-43 and an accumulation of large vesicles and membrane invaginations. However, we do not observe an increase in the number of clathrin-coated intermediates. We also note a depression in evoked excitatory junction potentials (EJPs) during high-rate stimulation, accompanied by aberrantly large miniature EJPs. The data reveal the important role of Dap160 in the targeting of dynamin to the periactive zone, where it is required to suppress bulk synaptic vesicle membrane retrieval during high-frequency activity.
authors: Department of Neuroscience, DBRM, Karolinska Institutet, von Eulers väg 3, 171 77 Stockholm, Sweden.
authors: Åsa M E
authors: ÅM
authors: Winther
authors: Wei
authors: W
authors: Jiao
authors: Olga
authors: O
authors: Vorontsova
authors: Kathryn A
authors: KA
authors: Rees
authors: Tong-Wey
authors: TW
authors: Koh
authors: Elena
authors: E
authors: Sopova
authors: Karen L
authors: KL
authors: Schulze
authors: Hugo J
authors: HJ
authors: Bellen
authors: Oleg
authors: O
authors: Shupliakov
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D007150:Immunohistochemistry; D009469:Neuromuscular Junction / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C113692:Dap160 protein, Drosophila; D029721:Drosophila Proteins; D033921:Vesicular Transport Proteins