Neurexins cluster Ca2+ channels within the presynaptic active zone.

The EMBO Journal
Fujun LuoThomas C Südhof

Abstract

To achieve ultrafast neurotransmission, neurons assemble synapses with highly organized presynaptic and postsynaptic nanomachines that are aligned by synaptic adhesion molecules. How functional assembly of presynaptic active zones is controlled via trans-synaptic interactions remains unknown. Here, we conditionally deleted all three neurexin adhesion molecules from presynaptic neurons of the calyx of Held in the mouse auditory system, a model synapse that allows precise biophysical analyses of synaptic properties. The pan-neurexin deletion had no effect on synapse development or the basic release machinery, but dramatically impaired fast neurotransmitter release. The overall properties of presynaptic calcium ion channels appeared normal, as reflected by the similar characteristics of calcium currents recorded at the nerve terminals. However, the pan-neurexin deletion significantly impaired the tight coupling of calcium influx to exocytosis, thereby suppressing neurotransmitter release. Furthermore, the pan-neurexin deletion reduced the function of calcium-activated BK potassium channels, whose activation depends on their tight association with presynaptic calcium channels. Together, these results suggest that neurexins perform ...Continue Reading

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Citations

May 8, 2020·Journal of Neurochemistry·Katherine BonnycastleMichael A Cousin
Jul 25, 2020·The Journal of Cell Biology·Anna J KhalajThomas C Südhof
Dec 20, 2020·Journal of Neuroscience Methods·Zijun Sun, Thomas C Südhof
Mar 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Mitsuharu Midorikawa, Mariko Miyata
Mar 24, 2021·Current Opinion in Genetics & Development·Marc V Fuccillo, ChangHui Pak
Jun 5, 2021·The Journal of Cell Biology·Thomas C Südhof
May 27, 2021·Proceedings of the National Academy of Sciences of the United States of America·ChangHui PakThomas C Südhof

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