Extracellular domains of α-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels

Weiqi Zhang, Astrid Rohlmann, Vardanush Sargsyan, Gayane Aramuni, Robert E Hammer, Thomas C. Südhof, Markus Missler

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Neurexins constitute a large family of highly variable cell-surface molecules that may function in synaptic transmission and/or synapse formation. Each of the three known neurexin genes encodes two major neurexin variants, α- and β-neurexins, that are composed of distinct extracellular domains linked to identical intracellular sequences. Deletions of one, two, or all three α-neurexins in mice recently demonstrated their essential role at synapses. In multiple α-neurexin knock-outs, neurotransmitter release from excitatory and inhibitory synapses was severely reduced, primarily probably because voltage-dependent Ca2+ channels were impaired. It remained unclear, however, which neurexin variants actually influence exocytosis and Ca2+ channels, which domain of neurexins is required for this function, and which Ca2+-channel subtypes are regulated. Here, we show by electrophysiological recordings that transgenic neurexin 1α rescues the release and Ca2+-current phenotypes, whereas transgenic neurexin 1β has no effect, indicating the importance of the extracellular sequences for the function of neurexins. Because neurexin 1α rescued the knock-out phenotype independent of the α-neurexin gene deleted, these data are consistent with a redundant function among different α-neurexins. In both knock-out and transgenically rescued mice, α-neurexins selectively affected the component of neurotransmitter release that depended on activation of N- and P/Q-type Ca2+ channels, but left L-type Ca2+ channels unscathed. Our findings indicate that α-neurexins represent organizer molecules in neurotransmission that regulate N- and P/Q-type Ca 2+ channels, constituting an essential role at synapses that critically involves the extracellular domains of neurexins.

Original languageEnglish (US)
Pages (from-to)4330-4342
Number of pages13
JournalJournal of Neuroscience
Volume25
Issue number17
DOIs
StatePublished - Apr 27 2005

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Keywords

  • Brainstem
  • Calcium channels
  • Cell adhesion
  • Synapse
  • Transgenic mouse
  • Transmission

ASJC Scopus subject areas

  • Neuroscience(all)

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