Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking
Autor/a
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
Fecha de publicación
2020ISSN
0021-9525
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
61 - Medicina
616.8 - Neurología. Neuropatología. Sistema nervioso
Palabras clave
Neurociències
Neurones
Cervell
Neuroplasticitat
Neurociencias
Neuronas
Cerebro
Neuroplasticidad
Neurosciences
Neurons
Brain
Neuroplasticity
Páginas
31
Publicado por
Rockefeller University Press
Colección
219; 10
Publicado en
Journal of Cell Biology
Citación
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
Número del acuerdo de la subvención
info:eu-repo/grantAgreement/ES/2PE/SAF2017-82813-C3-3R
info:eu-repo/grantAgreement/ES/2PE/SAF2017-89271-R
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Derechos
© 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/).
Excepto si se señala otra cosa, la licencia del ítem se describe como https://creativecommons.org/licenses/by-nc-sa/4.0/