SNX27-Mediated Recycling of Neuroligin-2 Regulates Inhibitory Signaling
Els F Halff1, Blanka R Szulc1, Flavie Lesept1
1Department of Neuroscience, Physiology, and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Abstract:
GABAA receptors mediate fast inhibitory transmission in the brain, and their number can be rapidly up- or downregulated to alter synaptic strength. Neuroligin-2 plays a critical role in the stabilization of synaptic GABAA receptors and the development and maintenance of inhibitory synapses. To date, little is known about how the amount of neuroligin-2 at the synapse is regulated and whether neuroligin-2 trafficking affects inhibitory signaling. Here, we show that neuroligin-2, when internalized to endosomes, co-localizes with SNX27, a brain-enriched cargo-adaptor protein that facilitates membrane protein recycling. Direct interaction between the PDZ domain of SNX27 and PDZ-binding motif in neuroligin-2 enables membrane retrieval of neuroligin-2, thus enhancing synaptic neuroligin-2 clusters. Furthermore, SNX27 knockdown has the opposite effect. SNX27-mediated up- and downregulation of neuroligin-2 surface levels affects inhibitory synapse composition and signaling strength. Taken together, we show a role for SNX27-mediated recycling of neuroligin-2 in maintenance and signaling of the GABAergic synapse.
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Synaptic Signaling
Most synapses are chemical, meaning an electrical impulse or action potential spurs the release of chemical messengers called neurotransmitters. The neuron sending the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron.
The presynaptic neuron fires an action potential that...
Synaptic Signaling
