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Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid

Author

Listed:
  • Anne Schmidt

    (Max-Planck-Institute of Molecular Cell Biology and Genetics
    University of Heidelberg)

  • Michael Wolde

    (University of Göttingen, and Max-Planck-Institute of Biophysical Chemistry)

  • Christoph Thiele

    (Max-Planck-Institute of Molecular Cell Biology and Genetics
    University of Heidelberg)

  • Werner Fest

    (University of Göttingen, and Max-Planck-Institute of Biophysical Chemistry)

  • Hartmut Kratzin

    (Max-Planck-Institute for Experimental Medicine)

  • Alexandre V. Podtelejnikov

    (European Molecular Biology Laboratory
    University of Southern Denmark)

  • Walter Witke

    (European Molecular Biology Laboratory
    European Molecular Biology Laboratory)

  • Wieland B. Huttner

    (Max-Planck-Institute of Molecular Cell Biology and Genetics
    University of Heidelberg)

  • Hans-Dieter Söling

    (University of Göttingen, and Max-Planck-Institute of Biophysical Chemistry)

Abstract

Endophilin I is a presynaptic protein of unknown function that binds to dynamin, a GTPase that is implicated in endocytosis and recycling of synaptic vesicles. Here we show that endophilin I is essential for the formation of synaptic-like microvesicles (SLMVs) from the plasma membrane. Endophilin I exhibits lysophosphatidic acid acyl transferase (LPAAT) activity, and endophilin-I-mediated SLMV formation requires the transfer of the unsaturated fatty acid arachidonate to lysophosphatidic acid, converting it to phosphatidic acid. A deletion mutant lacking the SH3 domain through which endophilin I interacts with dynamin still exhibits LPAAT activity but no longer mediates SLMV formation. These results indicate that endophilin I may induce negative membrane curvature by converting an inverted-cone-shaped lipid to a cone-shaped lipid in the cytoplasmic leaflet of the bilayer. We propose that, through this action, endophilin I works with dynamin to mediate synaptic vesicle invagination from the plasma membrane and fission.

Suggested Citation

  • Anne Schmidt & Michael Wolde & Christoph Thiele & Werner Fest & Hartmut Kratzin & Alexandre V. Podtelejnikov & Walter Witke & Wieland B. Huttner & Hans-Dieter Söling, 1999. "Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid," Nature, Nature, vol. 401(6749), pages 133-141, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6749:d:10.1038_43613
    DOI: 10.1038/43613
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