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

  1. Azam Razzaq1,2,
  2. Iain M. Robinson1,
  3. Harvey T. McMahon3,
  4. Jeremy N. Skepper4,
  5. Ya Su1,7,
  6. Andrew C. Zelhof5,6,
  7. Antony P. Jackson2,
  8. Nicholas J. Gay2, and
  9. Cahir J. O'Kane1,8
  1. 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.

Keywords

Footnotes

  • 7 Present address: Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital Site, Hills Road, Cambridge CB2 2XY, UK.

  • 8 Corresponding author.

  • E-MAIL c.okane{at}gen.cam.ac.uk; FAX 44-1223-333992.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.207801.

    • Received May 10, 2001.
    • Accepted September 20, 2001.
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