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Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles

Author

Listed:
  • Enqi He

    (Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit (VU))

  • Keimpe Wierda

    (Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit (VU)
    Present address: VIB Center for the Biology of Disease, Leuven 3000, Belgium; Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium)

  • Rhode van Westen

    (Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU Medical Center)

  • Jurjen H. Broeke

    (Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU Medical Center)

  • Ruud F. Toonen

    (Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit (VU))

  • L. Niels Cornelisse

    (Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU Medical Center)

  • Matthijs Verhage

    (Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit (VU)
    Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU Medical Center)

Abstract

Synaptic transmission requires a stable pool of release-ready (primed) vesicles. Here we show that two molecules involved in SNARE-complex assembly, Munc13-1 and Munc18-1, together stabilize release-ready vesicles by preventing de-priming. Replacing neuronal Munc18-1 by a non-neuronal isoform Munc18-2 (Munc18-1/2SWAP) supports activity-dependent priming, but primed vesicles fall back into a non-releasable state (de-prime) within seconds. Munc13-1 deficiency produces a similar defect. Inhibitors of N-ethylmaleimide sensitive factor (NSF), N-ethylmaleimide (NEM) or interfering peptides, prevent de-priming in munc18-1/2SWAP or munc13-1 null synapses, but not in CAPS-1/2 null, another priming-deficient mutant. NEM rescues synaptic transmission in munc13-1 null and munc18-1/2SWAP synapses, in acute munc13-1 null slices and even partially in munc13-1/2 double null synapses. Together these data indicate that Munc13-1 and Munc18-1, but not CAPS-1/2, stabilize primed synaptic vesicles by preventing NSF-dependent de-priming.

Suggested Citation

  • Enqi He & Keimpe Wierda & Rhode van Westen & Jurjen H. Broeke & Ruud F. Toonen & L. Niels Cornelisse & Matthijs Verhage, 2017. "Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles," Nature Communications, Nature, vol. 8(1), pages 1-10, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15915
    DOI: 10.1038/ncomms15915
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    Cited by:

    1. 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.

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