Drosophila endosomal proteins hook and deep orange regulate synapse size but not synaptic vesicle recycling

To study the function of endosomes at synapses we analyzed the localization and function of two Drosophila endosomal proteins, Hook and Deep orange (D or), at the larval neuromuscular junction, Hook, a negative regulator of en docytic trafficking, and Dor, a positive regulator of endocytic trafficking , are highly enriched at synapses, especially close to postsynaptic membran es. Mutations in hook (hk) and dor do not affect synaptic vesicle recycling , as assessed by electrophysiological analysis of synaptic transmission and behavioral studies of double mutants with shi(ts) mutations that alter ves icle recycling, However, hk and dor mutations alter the number of presynapt ic varicosities (synapse size) in opposing ways, Synapse size is increased in hk(11) mutants and is decreased in dor(4) mutants. Double mutants for do r and hk show a dor-like phenotype, These effects on synapse size parallel known functions of Hook and Dor in endocytosis and strongly indicate a role for endocytic trafficking in the regulation of synapse size in vivo. Our o bservations suggest a model in which Hook and Dor function in later stages of endocytosis is essential for regulating synaptic plasma membrane composi tion but not synaptic vesicle recycling. (C) 2000 John Wiley & Sans, Inc.