Amphiphysin is necessary for organization of the excitation–contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila
- Azam Razzaq1,2,
- Iain M. Robinson1,
- Harvey T. McMahon3,
- Jeremy N. Skepper4,
- Ya Su1,7,
- Andrew C. Zelhof5,6,
- Antony P. Jackson2,
- Nicholas J. Gay2, and
- Cahir J. O'Kane1,8
- 1Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK; 2Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK; 3Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, UK; 4Multi-Imaging Centre, Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, UK; 5Institute of Neuroscience and Institute of Molecular Biology, Howard Hughes Medical Institution, University of Oregon, Eugene, Oregon 97403, USA; 6Department of Biology, Howard Hughes Medical Institution, University of California, San Diego, La Jolla, California 92093, USA
Abstract
Amphiphysins 1 and 2 are enriched in the mammalian brain and are proposed to recruit dynamin to sites of endocytosis. Shorter amphiphysin 2 splice variants are also found ubiquitously, with an enrichment in skeletal muscle. At the Drosophila larval neuromuscular junction, amphiphysin is localized postsynaptically andamphiphysin mutants have no major defects in neurotransmission; 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. Amphiphysinmutants have a novel phenotype, a severely disorganized T-tubule/sarcoplasmic reticulum system. We therefore propose that muscle amphiphysin is not involved in clathrin-mediated endocytosis, but in the structural organization of the membrane-bound compartments of the excitation–contraction coupling machinery of muscles.
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Footnotes
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↵7 Present address: Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital Site, Hills Road, Cambridge CB2 2XY, UK.
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↵8 Corresponding author.
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E-MAIL c.okane{at}gen.cam.ac.uk; FAX 44-1223-333992.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.207801.
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- Received May 10, 2001.
- Accepted September 20, 2001.
- Cold Spring Harbor Laboratory Press