SNARE protein SNAP25 regulates the chloride-transporter KCC2 in neurons

Inhibitory synaptic neurotransmission mediated by GABA requires a low concentration of chloride ions (Cl−) in neurons, which is established and maintained by the potassium-chloride co-transporter 2 (KCC2). While KCC2-interacting proteins are known to regulate KCC2 protein level and function, specifi...

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Veröffentlicht in:iScience 2024-11, Vol.27 (11), p.111156, Article 111156
Hauptverfasser: Raveendran, Vineeth Andisseryparambil, Serranilla, Melissa, Asgarihafshejani, Azam, de Saint-Rome, Miranda, Cherednychenko, Mariia, Mullany, Shanelle, Mitchell, Jennifer A., Pressey, Jessica C., Woodin, Melanie A.
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container_issue 11
container_start_page 111156
container_title iScience
container_volume 27
creator Raveendran, Vineeth Andisseryparambil
Serranilla, Melissa
Asgarihafshejani, Azam
de Saint-Rome, Miranda
Cherednychenko, Mariia
Mullany, Shanelle
Mitchell, Jennifer A.
Pressey, Jessica C.
Woodin, Melanie A.
description Inhibitory synaptic neurotransmission mediated by GABA requires a low concentration of chloride ions (Cl−) in neurons, which is established and maintained by the potassium-chloride co-transporter 2 (KCC2). While KCC2-interacting proteins are known to regulate KCC2 protein level and function, specific KCC2-interacting partners are still being identified and characterized. We asked whether SNAP25, an integral component of the SNARE-complex and a novel KCC2 interactor, regulates KCC2 protein and function in mice. We demonstrated that SNAP25 interacts with KCC2, and that this interaction is regulated by protein kinase C (PKC)-mediated phosphorylation. We also discovered that SNAP25 knockdown decreases total KCC2 in cortical neurons, and reduces the strength of synaptic inhibition, as demonstrated through a depolarization of the reversal potential for GABA (EGABA), indicating reduced KCC2 function. Our biochemical and electrophysiological data combined demonstrate that SNAP25 regulates KCC2 membrane expression and function, and in doing so, regulates inhibitory synaptic transmission. [Display omitted] •SNAP25 knockdown reduces surface and total KCC2•SNAP25 knockdown depolarizes EGABA and reduces Cl− driving force•KCC2-SNAP25 interaction is PKC-dependent•The KCC2 C-terminus plays a prominent role in KCC2-SNAP25 interaction Biological sciences; Neuroscience; Molecular neuroscience
doi_str_mv 10.1016/j.isci.2024.111156
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Molecular neuroscience
Neuroscience
title SNARE protein SNAP25 regulates the chloride-transporter KCC2 in neurons
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