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Synaptic tetraspan vesicle membrane proteins are conserved but not needed for synaptogenesis and neuronal function in Caenorhabditis elegans

  1. Christian Abraham *,
  2. Harald Hutter † , ‡ ,
  3. Mark T. Palfreyman § ,
  4. Gabriele Spatkowski *,
  5. Robby M. Weimer § , , ‖ ,
  6. Reinhard Windoffer *,
  7. Erik M. Jorgensen § , and
  8. Rudolf E. Leube * , **
  1. *Department of Anatomy and Cell Biology, Johannes Gutenberg University, Becherweg 13, 55128 Mainz, Germany;
  2. †Max-Planck-Institut für Medizinische Forschung, Jahnstrasse 29, 69120 Heidelberg, Germany;
  3. §Department of Biology and Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112-0840; and
  4. Biologie Cellulaire de la Synapse, Ecole Normale Supérieure, 75005 Paris, France

  1. Edited by Pietro V. De Camilli, Yale University School of Medicine, New Haven, CT, and approved April 3, 2006 (received for review October 31, 2005)

Abstract

Tetraspan vesicle membrane proteins (TVPs) comprise a major portion of synaptic vesicle proteins, yet their contribution to the synaptic vesicle cycle is poorly understood. TVPs are grouped in three mammalian gene families: physins, gyrins, and secretory carrier-associated membrane proteins (SCAMPs). In Caenorhabditis elegans, only a single member of each of these families exists. These three nematode TVPs colocalize to the same vesicular compartment when expressed in mammalian cells, suggesting that they could serve overlapping functions. To examine their function, C. elegans null mutants were isolated for each gene, and a triple mutant was generated. Surprisingly, these animals develop normally and exhibit normal neuronal architecture and synaptic contacts. In addition, functions of the motor and sensory systems are normal as determined by pharmacological, chemotaxis, and thermotaxis assays. Finally, direct electrophysiological analysis of the neuromuscular junction revealed no phenotype in the TVP mutants. We therefore conclude that TVPs are not needed for the basic neuronal machinery and instead may contribute to subtle higher order functions.

Footnotes

  • **To whom correspondence should be addressed. E-mail: leube{at}uni-mainz.de

  • ↵ ‡Current address: Department of Biological Sciences, Simon Fraser University, BC, Canada V5A 1S6.

  • ↵ ‖Current address: Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.

  • Author contributions: C.A., H.H., R.W., E.M.J., and R.E.L. designed research; C.A., H.H., M.T.P., G.S., R.M.W., R.W., and R.E.L. performed research; C.A., H.H., M.T.P., G.S., R.M.W, R.W., and R.E.L. analyzed data; and C.A., M.T.P., E.M.J., and R.E.L. wrote the paper.

  • Conflict of interest statement: No conflicts declared.

  • This paper was submitted directly (Track II) to the PNAS office.

  • Abbreviations:

    Abbreviations:

    SCAMP,
    secretory carrier-associated membrane protein;
    TVP,
    tetraspan vesicle membrane protein.

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