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 (Dor), at the larval neuromuscular junction. Hook, a negative regulator of endocytic trafficking, and Dor, a positive regulator of endocytic trafficking, are highly enriched at synapses, especially close to postsynaptic membranes. 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 vesicle recycling. However, hk and dor mutations alter the number of presynaptic varicosities (synapse size) in opposing ways. Synapse size is increased in hk(11) mutants and is decreased in dor(4) mutants. Double mutants for dor 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 observations suggest a model in which Hook and Dor function in later stages of endocytosis is essential for regulating synaptic plasma membrane composition but not synaptic vesicle recycling.
Narayanan
R
R
Department of Molecular and Cellular Biology and ARL, Division of Neurobiology, University of Arizona, Life Sciences South, Box 210106, Tucson, Arizona 85721, USA. rnarayan@u.arizona.edu
Krämer
H
H
Ramaswami
M
M
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D048429:Cell Size / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D004330:Drosophila / Q000166:cytology / Q000378:metabolism; D029721:Drosophila Proteins; D004705:Endocytosis / Q000235:genetics; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology; D010243:Paralysis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020127:Recovery of Function / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins
D015816:Cell Adhesion Molecules, Neuronal; D004268:DNA-Binding Proteins; C104790:DOR protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D033921:Vesicular Transport Proteins; C051642:fasciclin II; C100411:hook protein, Drosophila