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Kusch, Valentin [Author]; Bornschein, Grit [Author]; Loreth, Desirée [Author]; Bank, Julia [Author]; Jordan, Joannes [Author]; Baur, David [Author]; Watanabe, Masahiko [Author]; Kulik, Akos [Author]; Heckmann, Manfred [Author]; Eilers, Jens-Karl [Author]; Schmidt, Hartmut [Author]

Munc13-3 is required for the developmental localization of Ca 2+ channels to active zones and the nanopositioning of Ca v 2.1 near release sensors

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  • Media type: E-Book; Special Print
  • Title: Munc13-3 is required for the developmental localization of Ca 2+ channels to active zones and the nanopositioning of Ca v 2.1 near release sensors
  • Contributor: Kusch, Valentin [VerfasserIn]; Bornschein, Grit [VerfasserIn]; Loreth, Desirée [VerfasserIn]; Bank, Julia [VerfasserIn]; Jordan, Joannes [VerfasserIn]; Baur, David [VerfasserIn]; Watanabe, Masahiko [VerfasserIn]; Kulik, Akos [VerfasserIn]; Heckmann, Manfred [VerfasserIn]; Eilers, Jens-Karl [VerfasserIn]; Schmidt, Hartmut [VerfasserIn]
  • imprint: New York, NY: Elsevier BV, 2018
  • Published in: Cell reports ; 22, 8 (2018), 1965-1973
  • Extent: 1 Online-Ressource (10 Seiten); Diagramme; Supplemental information
  • Language: English
  • DOI: 10.1016/j.celrep.2018.02.010
  • ISSN: 2211-1247
  • Identifier:
  • Origination:
  • Footnote:
  • Description: Abstract: Spatial relationships between Cav channels and release sensors at active zones (AZs) are a major determinant of synaptic fidelity. They are regulated developmentally, but the underlying molecular mechanisms are largely unclear. Here, we show that Munc13-3 regulates the density of Cav2.1 and Cav2.2 channels, alters the localization of Cav2.1, and is required for the development of tight, nanodomain coupling at parallel-fiber AZs. We combined EGTA application and Ca2+-channel pharmacology in electrophysiological and two-photon Ca2+ imaging experiments with quantitative freeze-fracture immunoelectron microscopy and mathematical modeling. We found that a normally occurring developmental shift from release being dominated by Ca2+ influx through Cav2.1 and Cav2.2 channels with domain overlap and loose coupling (microdomains) to a nanodomain Cav2.1 to sensor coupling is impaired in Munc13-3-deficient synapses. Thus, at AZs lacking Munc13-3, release remained triggered by Cav2.1 and Cav2.2 microdomains, suggesting a critical role of Munc13-3 in the formation of release sites with calcium channel nanodomains
  • Access State: Open Access