Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking
Author
Fadó Andrés, Rut
Domínguez, José Luis
Roig, Aina
Kaku, Moena
Chohnan, Shigeru
Solé, Montse
Unzeta, Mercedes
Miñano Molina, Alfredo Jesús
Rodríguez-Álvarez, José
Dickson, Eamonn James
Casals i Farré, Núria
Publication date
2020ISSN
0021-9525
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
616.8 - Neurology. Neuropathology. Nervous system
Keywords
Neurociències
Neurones
Cervell
Neuroplasticitat
Neurociencias
Neuronas
Cerebro
Neuroplasticidad
Neurosciences
Neurons
Brain
Neuroplasticity
Pages
31
Publisher
Rockefeller University Press
Collection
219; 10
Is part of
Journal of Cell Biology
Citation
Casas, Maria; Fadó, Rut; Domínguez, Jose Luis [et al.]. Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking. Journal of Cell Biology, 2020, 219(10), e201912045. Disponible en: <https://rupress.org/jcb/article/219/10/e201912045/152088/Sensing-of-nutrients-by-CPT1C-controls-SAC1>. Fecha de acceso: 3 nov. 2020. DOI: 10.1083/jcb.201912045
Grant agreement number
info:eu-repo/grantAgreement/ES/2PE/SAF2017-82813-C3-3R
info:eu-repo/grantAgreement/ES/2PE/SAF2017-89271-R
This item appears in the following Collection(s)
- Ciències de la Salut [740]
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/).
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-sa/4.0/