Affiliation:
1. Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, UK.
2. Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok 10210, Thailand.
Abstract
The trans-synaptic adhesion molecule neuroligin-2 (NL2) is essential for the development and function of inhibitory synapses. NL2 recruits the postsynaptic scaffold protein gephyrin, which, in turn, stabilizes γ-aminobutyric acid type A receptors (GABA
A
Rs) in the postsynaptic domain. Thus, the amount of NL2 at the synapse can control synaptic GABA
A
R concentration to tune inhibitory neurotransmission efficacy. Here, using biochemistry, imaging, single-particle tracking, and electrophysiology, we uncovered a key role for cAMP-dependent protein kinase (PKA) in the synaptic stabilization of NL2. We found that PKA-mediated phosphorylation of NL2 at Ser
714
caused its dispersal from the synapse and reduced NL2 surface amounts, leading to a loss of synaptic GABA
A
Rs. Conversely, enhancing the stability of NL2 at synapses by abolishing PKA-mediated phosphorylation led to increased inhibitory signaling. Thus, PKA plays a key role in regulating NL2 function and GABA-mediated synaptic inhibition.
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
4 articles.
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