Neurexins regulate presynaptic GABAB-receptors at central synapses

Fujun Luo (), Alessandra Sclip, Sean Merrill and Thomas C. Südhof
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Fujun Luo: Stanford University Medical School
Alessandra Sclip: Stanford University Medical School
Sean Merrill: Stanford University Medical School
Thomas C. Südhof: Stanford University Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Diverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABAB-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABAB-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABAB-receptor signaling complexes. At four model synapses, excitatory calyx of Held synapses in the brainstem, excitatory and inhibitory synapses on hippocampal CA1-region pyramidal neurons, and inhibitory basket cell synapses in the cerebellum, deletion of neurexins rendered neurotransmitter release significantly less sensitive to GABAB-receptor activation. Moreover, deletion of neurexins caused a loss of GABAB-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABAB-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.

Date: 2021
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DOI: 10.1038/s41467-021-22753-5

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