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Different domains of synaptotagmin control the choice between kiss-and-run and full fusion

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  • Chih-Tien Wang

    (University of Wisconsin–Madison)

  • Juu-Chin Lu

    (University of Wisconsin–Madison)

  • Jihong Bai

    (Biophysics Program, University of Wisconsin–Madison)

  • Payne Y. Chang

    (Biophysics Program, University of Wisconsin–Madison)

  • Thomas F. J. Martin

    (University of Wisconsin–Madison)

  • Edwin R. Chapman

    (University of Wisconsin–Madison)

  • Meyer B. Jackson

    (University of Wisconsin–Madison)

Abstract

Exocytosis—the release of the contents of a vesicle—proceeds by two mechanisms1,2,3,4,5,6. Full fusion occurs when the vesicle and plasma membranes merge. Alternatively, in what is termed kiss-and-run, vesicles can release transmitter during transient contacts with the plasma membrane. Little is known at the molecular level about how the choice between these two pathways is regulated. Here we report amperometric recordings of catecholamine efflux through individual fusion pores. Transfection with synaptotagmin (Syt) IV increased the frequency and duration of kiss-and-run events, but left their amplitude unchanged. Endogenous Syt IV, induced by forskolin treatment, had a similar effect. Full fusion was inhibited by mutation of a Ca2+ ligand in the C2A domain of Syt I; kiss-and-run was inhibited by mutation of a homologous Ca2+ ligand in the C2B domain of Syt IV. The Ca2+ sensitivity for full fusion was 5-fold higher with Syt I than Syt IV, but for kiss-and-run the Ca2+ sensitivities differed by a factor of only two. Syt thus regulates the choice between full fusion and kiss-and-run, with Ca2+ binding to the C2A and C2B domains playing an important role in this choice.

Suggested Citation

  • Chih-Tien Wang & Juu-Chin Lu & Jihong Bai & Payne Y. Chang & Thomas F. J. Martin & Edwin R. Chapman & Meyer B. Jackson, 2003. "Different domains of synaptotagmin control the choice between kiss-and-run and full fusion," Nature, Nature, vol. 424(6951), pages 943-947, August.
    • Handle: RePEc:nat:nature:v:424:y:2003:i:6951:d:10.1038_nature01857
    DOI: 10.1038/nature01857
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    Cited by:

    1. Ling-Gang Wu & Chung Yu Chan, 2024. "Membrane transformations of fusion and budding," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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