Halff, Els F;
Hannan, Saad;
Kwanthongdee, Jaturon;
Lesept, Flavie;
Smart, Trevor G;
Kittler, Josef T;
(2022)
Phosphorylation of neuroligin-2 by PKA regulates its cell surface abundance and synaptic stabilization.
Science Signaling
, 15
(739)
, Article eabg2505. 10.1126/scisignal.abg2505.
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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 (GABAARs) in the postsynaptic domain. Thus, the amount of NL2 at the synapse can control synaptic GABAAR 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 Ser714 caused its dispersal from the synapse and reduced NL2 surface amounts, leading to a loss of synaptic GABAARs. 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.
| Type: | Article |
|---|---|
| Title: | Phosphorylation of neuroligin-2 by PKA regulates its cell surface abundance and synaptic stabilization |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1126/scisignal.abg2505 |
| Publisher version: | https://doi.org/10.1126/scisignal.abg2505 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Cell Adhesion Molecules, Neuronal, Nerve Tissue Proteins, Phosphorylation, Receptors, GABA-A, Synapses, Synaptic Transmission, gamma-Aminobutyric Acid |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10153349 |
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