Neurexins regulate presynaptic GABA<sub>B</sub>-receptors at central synapses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33888718.
- Also identified by DOI 10.1038/s41467-021-22753-5 and PMC identifier 8062527.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Diverse signaling complexes are precisely assembled at the presynaptic active zone for dynamic modulation of synaptic transmission and synaptic plasticity. Presynaptic GABA<sub>B</sub>-receptors nucleate critical signaling complexes regulating neurotransmitter release at most synapses. However, the molecular mechanisms underlying assembly of GABA<sub>B</sub>-receptor signaling complexes remain unclear. Here we show that neurexins are required for the localization and function of presynaptic GABA<sub>B</sub>-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 GABA<sub>B</sub>-receptor activation. Moreover, deletion of neurexins caused a loss of GABA<sub>B</sub>-receptors from the presynaptic active zone of the calyx synapse. These findings extend the role of neurexins at the presynaptic active zone to enabling GABA<sub>B</sub>-receptor signaling, supporting the notion that neurexins function as central organizers of active zone signaling complexes.
Medical subject headings
- Calcium-Binding Proteins
- Nerve Tissue Proteins
- Neural Cell Adhesion Molecules
- Receptors, GABA-B
- Synapses