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Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles

Author

Listed:
  • Iris Augustin

    (Max-Planck-Institut für Experimentelle Medizin, AG Molekulare Neurobiologie)

  • Christian Rosenmund

    (Max-Planck-Institut fr Biophysikalische Chemie)

  • Thomas C. Südhof

    (Center for Basic Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center)

  • Nils Brose

    (Max-Planck-Institut für Experimentelle Medizin, AG Molekulare Neurobiologie)

Abstract

Neurotransmitter release at synapses between nerve cells is mediated by calcium-triggered exocytotic fusion of synaptic vesicles1. Before fusion, vesicles dock at the presynaptic release site where they mature to a fusion-competent state1,2. Here we identify Munc13-1, a brain-specific presynaptic phorbol ester receptor3,4, as an essential protein for synaptic vesicle maturation. We show that glutamatergic hippocampal neurons from mice lacking Munc13-1 form ultrastructurally normal synapses whose synaptic-vesicle cycle is arrested at the maturation step. Transmitter release from mutant synapses cannot be triggered by action potentials, calcium-ionophores or hypertonic sucrose solution. In contrast, release evoked by α-latrotoxin is indistinguishable from wild-type controls, indicating that the toxin can bypass Munc13-1-mediated vesicle maturation. A small subpopulation of synapses of any given glutamatergic neuron as well as all synapses of GABA (γ-aminobutyric acid)-containing neurons are unaffected by Munc13-1 loss, demonstrating the existence of multiple and transmitter-specific synaptic vesicle maturation processes in synapses.

Suggested Citation

  • Iris Augustin & Christian Rosenmund & Thomas C. Südhof & Nils Brose, 1999. "Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles," Nature, Nature, vol. 400(6743), pages 457-461, July.
  • Handle: RePEc:nat:nature:v:400:y:1999:i:6743:d:10.1038_22768
    DOI: 10.1038/22768
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    1. Santiago Mora & Anna Stuckert & Rasmus Huth Friis & Kimberly Pietersz & Gith Noes-Holt & Roser Montañana-Rosell & Haoyu Wang & Andreas Toft Sørensen & Raghavendra Selvan & Joost Verhaagen & Ilary Allo, 2024. "Stabilization of V1 interneuron-motor neuron connectivity ameliorates motor phenotype in a mouse model of ALS," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. 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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