Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/105790
Title: Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus
Author: Fadó Andres, Rut
Soto del Cerro, David
Miñano Molina, Alfredo J.
Pozo, Macarena
Carrasco, Patricia
Yefimenko Nosova, Natalia
Rodríguez Álvarez, José
Casals i Farré, Núria
Keywords: Sinapsi
Àcid glutàmic
Biologia molecular
Hipocamp (Cervell)
Synapses
Glutamic acid
Molecular biology
Hippocampus (Brain)
Issue Date: 16-Oct-2015
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: The regulation of AMPA-type receptor (AMPAR) abundance in the postsynaptic membrane is an important mechanism involved in learning and memory formation. Recent data suggest that one of the constituents of the AMPAR complex is carnitine palmitoyltransferase 1C (CPT1C), a brain-specific isoform located in the endoplasmic reticulum of neurons. Previous results had demonstrated that CPT1C deficiency disrupted spine maturation in hippocampal neurons and impaired spatial learning, but the role of CPT1C in AMPAR physiology had remained mostly unknown. In the present study, we show that CPT1C binds GluA1 and GluA2 and that the three proteins have the same expression profile during neuronal maturation. Moreover, in hippocampal neurons of CPT1C KO mice, AMPAR-mediated miniature excitatory postsynaptic currents and synaptic levels of AMPAR subunits GluA1 and GluA2 are significantly reduced. We show that AMPAR expression is dependent on CPT1C levels because total protein levels of GluA1 and GluA2 are decreased in CPT1C KO neurons and are increased in CPT1C-overexpressing neurons, whereas other synaptic proteins remain unaltered. Notably, mRNA levels of AMPARs remained unchanged in those cultures, indicating that CPT1C is post-transcriptionally involved. We demonstrate that CPT1C is directly involved in the de novo synthesis of GluA1 and not in protein degradation. Moreover, in CPT1C KO cultured neurons, GluA1 synthesis after chemical long term depression was clearly diminished, and brain-derived neurotrophic factor treatment was unable to phosphorylate the mammalian target of rapamycin (mTOR) and stimulate GluA1 protein synthesis. These data newly identify CPT1C as a regulator of AMPAR translation efficiency and therefore also synaptic function in the hippocampus.
Note: Reproducció del document publicat a: https://doi.org/10.1074/jbc.M115.681064
It is part of: Journal of Biological Chemistry, 2015, vol. 290, num. 42, p. 25548-25560
Related resource: https://doi.org/10.1074/jbc.M115.681064
URI: http://hdl.handle.net/2445/105790
ISSN: 0021-9258
Appears in Collections:Articles publicats en revistes (Biomedicina)

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