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Allosteric modulation of the presynaptic Ca2+ sensor for vesicle fusion

Author

Listed:
  • Xuelin Lou

    (Max-Planck-Institut für biophysikalische Chemie)

  • Volker Scheuss

    (Max-Planck-Institut für biophysikalische Chemie
    Cold Spring Harbor Laboratory)

  • Ralf Schneggenburger

    (Max-Planck-Institut für biophysikalische Chemie)

Abstract

Neurotransmitter release is triggered by an increase in the cytosolic Ca2+ concentration ([Ca2+]i), but it is unknown whether the Ca2+-sensitivity of vesicle fusion is modulated during synaptic plasticity. We investigated whether the potentiation of neurotransmitter release by phorbol esters1,2,3, which target presynaptic protein kinase C (PKC)/munc-13 signalling cascades4,5,6, exerts a direct effect on the Ca2+-sensitivity of vesicle fusion. Using direct presynaptic Ca2+-manipulation and Ca2+ uncaging at a giant presynaptic terminal, the calyx of Held, we show that phorbol esters potentiate transmitter release by increasing the apparent Ca2+-sensitivity of vesicle fusion. Phorbol esters potentiate Ca2+-evoked release as well as the spontaneous release rate. We explain both effects by an increased fusion ‘willingness’ in a new allosteric model of Ca2+-activation of vesicle fusion. In agreement with an allosteric mechanism, we observe that the classically high Ca2+ cooperativity in triggering vesicle fusion (∼ 4) is gradually reduced below 3 µM [Ca2+]i, reaching a value of

Suggested Citation

  • Xuelin Lou & Volker Scheuss & Ralf Schneggenburger, 2005. "Allosteric modulation of the presynaptic Ca2+ sensor for vesicle fusion," Nature, Nature, vol. 435(7041), pages 497-501, May.
    • Handle: RePEc:nat:nature:v:435:y:2005:i:7041:d:10.1038_nature03568
    DOI: 10.1038/nature03568
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    Cited by:

    1. Marieke Meijer & Miriam Öttl & Jie Yang & Aygul Subkhangulova & Avinash Kumar & Zicheng Feng & Torben W. Voorst & Alexander J. Groffen & Jan R. T. Weering & Yongli Zhang & Matthijs Verhage, 2024. "Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Philipe R. F. Mendonça & Erica Tagliatti & Helen Langley & Dimitrios Kotzadimitriou & Criseida G. Zamora-Chimal & Yulia Timofeeva & Kirill E. Volynski, 2022. "Asynchronous glutamate release is enhanced in low release efficacy synapses and dispersed across the active zone," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Romain Volmer & Céline Monnet & Daniel Gonzalez-Dunia, 2006. "Borna Disease Virus Blocks Potentiation of Presynaptic Activity through Inhibition of Protein Kinase C Signaling," PLOS Pathogens, Public Library of Science, vol. 2(3), pages 1-9, March.

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