The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling
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 activit...
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Nature Publishing Group
2025-07-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03438-9 |
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| author | Gareth Banks Malgorzata Cyranka Natascia Vedovato Charlotte Meller Alex Rawnsley Edward O. Mann Michelle Stewart Heidi de Wet |
| author_facet | Gareth Banks Malgorzata Cyranka Natascia Vedovato Charlotte Meller Alex Rawnsley Edward O. Mann Michelle Stewart Heidi de Wet |
| author_sort | Gareth Banks |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-16a7ef5b07ea44deac5df70740f857a2 |
| institution | DOAJ |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-16a7ef5b07ea44deac5df70740f857a22025-08-20T03:04:15ZengNature Publishing GroupTranslational Psychiatry2158-31882025-07-0115111210.1038/s41398-025-03438-9The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signallingGareth Banks0Malgorzata Cyranka1Natascia Vedovato2Charlotte Meller3Alex Rawnsley4Edward O. Mann5Michelle Stewart6Heidi de Wet7School of Science and Technology, Nottingham Trent UniversityDept of Physiology, Anatomy and Genetics, University of OxfordDept of Physiology, Anatomy and Genetics, University of OxfordDept of Physiology, Anatomy and Genetics, University of OxfordDept of Physiology, Anatomy and Genetics, University of OxfordDept of Physiology, Anatomy and Genetics, University of OxfordMRC Harwell Institute, Mary Lyon Centre, Harwell CampusDept of Physiology, Anatomy and Genetics, University of OxfordAbstract 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.https://doi.org/10.1038/s41398-025-03438-9 |
| spellingShingle | Gareth Banks Malgorzata Cyranka Natascia Vedovato Charlotte Meller Alex Rawnsley Edward O. Mann Michelle Stewart Heidi de Wet The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling Translational Psychiatry |
| title | The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling |
| title_full | The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling |
| title_fullStr | The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling |
| title_full_unstemmed | The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling |
| title_short | The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling |
| title_sort | murine atp binding cassette transporter c5 abcc5 mrp5 cmoat plays a role in memory consolidation circadian rhythm regulation and glutamatergic signalling |
| url | https://doi.org/10.1038/s41398-025-03438-9 |
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