Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila

Amphiphysins 1 and 2 are enriched in the mammalian brain and are proposed t o recruit dynamin to sites of endocytosis. Shorter amphiphysin 2 splice var iants are also found ubiquitously, with an enrichment in skeletal muscle. A t the Drosophila larval neuromuscular junction, amphiphysin is localized po stsynaptically and amphiphysin mutants have no major defects in neurotransm ission; they are also viable, but flightless. Like mammalian amphiphysin 2 in muscles, Drosophila amphiphysin does not bind clathrin, but can tubulate lipids and is localized on T-tubules. Amphiphysin mutants have a novel phe notype, a severely disorganized T-tubule/sarcoplasmic reticulum system. We therefore propose that muscle amphiphysin is not involved in clathrin-media ted endocytosis, but in the structural organization of the membrane-bound c ompartments of the excitation-contraction coupling machinery of muscles.