Extracellular Domains of α-Neurexins Participate in Regulating Synaptic Transmission by Selectively Affecting N- and P/Q-Type Ca2+ Channels
By Weiqi Zhang, A. Rohlmann, V. Sargsyan, G. Aramuni, R. Hammer, T. Sūdhof, M. Missler. Journal of Neuroscience, 2005
140 citations recorded by the source corpus.
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 Ca2+ channels, constituting an essential role at synapses that critically involves the extracellular domains of neurexins.
Subfields: Cell Biology, Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/003800d8d89dfba1f08640cd3aa49c844956a22f
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Citations in the corpus
- Neuroligins determine synapse maturation and function. (2006, unknown): “We examined the function of the brainstem respiratory network consisting of the pre-Bötzinger complex (PBC) and the hypoglossal nucleus (NH) in acute brainstem slices from triple KO mice by whole-cell patch-clamp recordings (Missler et al., 2003; Zhang et al., 2005).”
- Neuroligins and neurexins link synaptic function to cognitive disease (2008, background): “This impairment is both presynaptic and postsynaptic but is most significantly observed in action-potential-driven neurotransmitter release, which is severely depressed, largely because of a loss of presynaptic Ca 2p -channel functio”
- Neurexin-neuroligin signaling in synapse development. (2007, background): “Transmitter release that depends on N-type and P/Q-type Ca channels is severely reduced in these mutants [48].”
- Cell adhesion molecules: signalling functions at the synapse (2007, background): “The specificity of this phenotype to α-neurexin deletion was confirmed by rescue experiments in which calcium channel function was rescued by the transgenic expression of 1α-neurexin but not 1β-neurexi”