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Differential SNARE chaperoning by Munc13-1 and Munc18-1 dictates fusion pore fate at the release site

Author

Listed:
  • Bhavya R. Bhaskar

    (Tata Institute of Fundamental Research)

  • Laxmi Yadav

    (Tata Institute of Fundamental Research)

  • Malavika Sriram

    (Tata Institute of Fundamental Research)

  • Kinjal Sanghrajka

    (Tata Institute of Fundamental Research)

  • Mayank Gupta

    (Tata Institute of Fundamental Research)

  • Boby K. V

    (Tata Institute of Fundamental Research)

  • Rohith K. Nellikka

    (Tata Institute of Fundamental Research)

  • Debasis Das

    (Tata Institute of Fundamental Research)

Abstract

The regulated release of chemical messengers is crucial for cell-to-cell communication; abnormalities in which impact coordinated human body function. During vesicular secretion, multiple SNARE complexes assemble at the release site, leading to fusion pore opening. How membrane fusion regulators act on heterogeneous SNARE populations to assemble fusion pores in a timely and synchronized manner, is unknown. Here, we demonstrate the role of SNARE chaperones Munc13-1 and Munc18-1 in rescuing individual nascent fusion pores from their diacylglycerol lipid-mediated inhibitory states. At the onset of membrane fusion, Munc13-1 clusters multiple SNARE complexes at the release site and synchronizes release events, while Munc18-1 stoichiometrically interacts with trans-SNARE complexes to enhance N- to C-terminal zippering. When both Munc proteins are present simultaneously, they differentially access dynamic trans-SNARE complexes to regulate pore properties. Overall, Munc proteins’ direct action on fusion pore assembly indicates their role in controlling quantal size during vesicular secretion.

Suggested Citation

  • Bhavya R. Bhaskar & Laxmi Yadav & Malavika Sriram & Kinjal Sanghrajka & Mayank Gupta & Boby K. V & Rohith K. Nellikka & Debasis Das, 2024. "Differential SNARE chaperoning by Munc13-1 and Munc18-1 dictates fusion pore fate at the release site," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46965-7
    DOI: 10.1038/s41467-024-46965-7
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    References listed on IDEAS

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