Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking
Autor/a
Rut, Fadó
Domínguez, José Luis
Roig, Aina
Kaku, Moena
Chohnan, Shigeru
Solé, Montse
Unzeta, Mercedes
Miñano Molina, Alfredo Jesús
Rodríguez-Álvarez, José
James Dickson, Eamonn
Casals i Farré, Núria
Data de publicació
2020-09ISSN
0021-9525
Resum
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.
Tipus de document
Article
Versió del document
Versió publicada
Llengua
English
Matèries (CDU)
61 - Medicina
Paraules clau
Neurociències
Neurones
Cervell
Glucosa
Cognició
Neurociencias
Neuronas
Cerebro
Glucosa
Cognición
Neurosciences
Neurons
Brain
Glucose
Cognition
Pàgines
31
Publicat per
Rockefeller University Press
Col·lecció
219; 10
Publicat a
Journal of Cell Biology
Número de l'acord de la subvenció
info:eu-repo/grantAgreement/ES/2PE/SAF2017-82813-C3-3R
info:eu-repo/grantAgreement/ES/2PE/SAF2017-89271-R
Aquest element apareix en la col·lecció o col·leccions següent(s)
- Ciències de la Salut [736]
Drets
© 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/).
Excepte que s'indiqui una altra cosa, la llicència de l'ítem es descriu com https://creativecommons.org/licenses/by-nc-sa/4.0/