The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling

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Banks, G ORCID: https://orcid.org/0000-0002-8647-667X, Cyranka, M, Vedovato, N, Meller, C, Rawnsley, A, Mann, EO, Stewart, M and de Wet, H, 2025. The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling. Translational Psychiatry, 15: 218. ISSN 2158-3188

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Official URL: https://doi.org/10.1038/s41398-025-03438-9

Abstract

ATP-Binding cassette (ABC) transporters are a family of integral membrane ATPases that transport a large number of structurally unrelated compounds. The physiological role of the orphan transporter Abcc5 remains poorly understood. As previous work demonstrated that the loss of Abcc5 activity leads to elevated levels of NAAG in the brain, the impact of Abcc5 ablation was ascertained using behavioural phenotyping, circadian rhythm analysis and electrophysiological recordings of brain slices from Abcc5−/− mice and compared to wild-type littermates. Behavioural phenotyping of Abcc5−/− mice shows that the loss of murine Abcc5 activity results in profound changes in pre-pulse inhibition (PPI) as well as altered memory consolidation. Circadian measures of activity showed a delay in the timing of Abcc5−/− mice activity rhythm peak. Additionally, activity defined sleep analysis highlighted differences in sleep patterns in Abcc5−/− mice compared to wild-type controls. Patch clamp recording from pyramidal cells in the 2/3 layer of the frontal cortex showed altered synaptic AMPA/NMDA receptor current ratios and increased frequency of spontaneous excitatory postsynaptic currents (sEPSC). This study demonstrates that the loss of functional Abcc5 transporters does have behavioural consequences in mammals and alters NMDA receptor activity. These results highlight a previously unknown role of Abcc5 in the brain.

Item Type:	Journal article
Publication Title:	Translational Psychiatry
Creators:	Banks, G., Cyranka, M., Vedovato, N., Meller, C., Rawnsley, A., Mann, E.O., Stewart, M. and de Wet, H.
Publisher:	Springer Science and Business Media LLC
Date:	1 July 2025
Volume:	15
ISSN:	2158-3188
Identifiers:	Number Type 10.1038/s41398-025-03438-9 DOI 2463698 Other
Rights:	© The Author(s) 2025 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Divisions:	Schools > School of Science and Technology
Record created by:	Jeremy Silvester
Date Added:	04 Jul 2025 08:14
Last Modified:	04 Jul 2025 08:14
URI:	https://irep.ntu.ac.uk/id/eprint/53877