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Title:	Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking
Author:	Casas, Maria; 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
Notes:	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.
Subject(s):	-Neurociències -Neurones -Cervell -Neuroplasticitat -Neurociencias -Neuronas -Cerebro -Neuroplasticidad -Neurosciences -Neurons -Brain -Neuroplasticity -61 -616.8
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/). https://creativecommons.org/licenses/by-nc-sa/4.0/
Document type:	Article Article - Published version
Published by:	Rockefeller University Press
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