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Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking
dc.contributor.author | Casas, Maria | |
dc.contributor.author | Rut, Fadó | |
dc.contributor.author | Domínguez, José Luis | |
dc.contributor.author | Roig, Aina | |
dc.contributor.author | Kaku, Moena | |
dc.contributor.author | Chohnan, Shigeru | |
dc.contributor.author | Solé, Montse | |
dc.contributor.author | Unzeta, Mercedes | |
dc.contributor.author | Miñano Molina, Alfredo Jesús | |
dc.contributor.author | Rodríguez-Álvarez, José | |
dc.contributor.author | James Dickson, Eamonn | |
dc.contributor.author | Casals i Farré, Núria | |
dc.date.accessioned | 2020-10-21T17:35:32Z | |
dc.date.available | 2022-03-24T23:45:12Z | |
dc.date.issued | 2020-09 | |
dc.identifier.issn | 0021-9525 | ca |
dc.identifier.uri | http://hdl.handle.net/20.500.12328/1689 | |
dc.description.abstract | Carnitine palmitoyltransferase 1C (CPT1C) is a sensor of malonyl-CoA and is located in the ER of neurons. AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the brain and play a key role in synaptic plasticity. In the present study, we demonstrate across different metabolic stress conditions that modulate malonyl-CoA levels in cortical neurons that CPT1C regulates the trafficking of the major AMPAR subunit, GluA1, through the phosphatidyl-inositol-4-phosphate (PI(4)P) phosphatase SAC1. In normal conditions, CPT1C down-regulates SAC1 catalytic activity, allowing efficient GluA1 trafficking to the plasma membrane. However, under low malonyl-CoA levels, such as during glucose depletion, CPT1C-dependent inhibition of SAC1 is released, facilitating SAC1’s translocation to ER-TGN contact sites to decrease TGN PI(4)P pools and trigger GluA1 retention at the TGN. Results reveal that GluA1 trafficking is regulated by CPT1C sensing of malonyl-CoA and provide the first report of a SAC1 inhibitor. Moreover, they shed light on how nutrients can affect synaptic function and cognition. | ca |
dc.format.extent | 31 | ca |
dc.language.iso | eng | ca |
dc.publisher | Rockefeller University Press | ca |
dc.relation.ispartof | Journal of Cell Biology | ca |
dc.relation.ispartofseries | 219;10 | |
dc.rights | © 2020 Casas et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). | ca |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-sa/4.0/ | |
dc.subject.other | Neurociències | ca |
dc.subject.other | Neurones | |
dc.subject.other | Cervell | |
dc.subject.other | Glucosa | |
dc.subject.other | Cognició | |
dc.subject.other | Neurociencias | |
dc.subject.other | Neuronas | |
dc.subject.other | Cerebro | |
dc.subject.other | Glucosa | |
dc.subject.other | Cognición | |
dc.subject.other | Neurosciences | |
dc.subject.other | Neurons | |
dc.subject.other | Brain | |
dc.subject.other | Glucose | |
dc.subject.other | Cognition | |
dc.title | Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking | ca |
dc.type | info:eu-repo/semantics/article | ca |
dc.description.version | info:eu-repo/semantics/publishedVersion | ca |
dc.rights.accessLevel | info:eu-repo/semantics/openAccess | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/2PE/SAF2017-82813-C3-3R | |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/2PE/SAF2017-89271-R | |
dc.subject.udc | 61 | ca |
dc.identifier.doi | https://dx.doi.org/10.1083/jcb.201912045 | ca |
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