title: AMPAR interacting protein CPT1C enhances surface expression of GluA1-containing receptors.
abstract: AMPARs mediate the vast majority of fast excitatory synaptic transmission in the brain and their biophysical and trafficking properties depend on their subunit composition and on several posttranscriptional and posttranslational modifications. Additionally, in the brain AMPARs associate with auxiliary subunits, which modify the properties of the receptors. Despite the abundance of AMPAR partners, recent proteomic studies have revealed even more interacting proteins that could potentially be involved in AMPAR regulation. Amongst these, carnitine palmitoyltransferase 1C (CPT1C) has been demonstrated to form an integral part of native AMPAR complexes in brain tissue extracts. Thus, we aimed to investigate whether CPT1C might be able to modulate AMPAR function. Firstly, we confirmed that CPT1C is an interacting protein of AMPARs in heterologous expression systems. Secondly, CPT1C enhanced whole-cell currents of GluA1 homomeric and GluA1/GluA2 heteromeric receptors. However, CPT1C does not alter the biophysical properties of AMPARs and co-localization experiments revealed that AMPARs and CPT1C are not associated at the plasma membrane despite a strong level of co-localization at the intracellular level. We established that increased surface GluA1 receptor number was responsible for the enhanced AMPAR mediated currents in the presence of CPT1C. Additionally, we revealed that the palmitoylable residue C585 of GluA1 is important in the enhancement of AMPAR trafficking to the cell surface by CPT1C. Nevertheless, despite its potential as a depalmitoylating enzyme, CPT1C does not affect the palmitoylation state of GluA1. To sum up, this work suggests that CPT1C plays a role as a novel regulator of AMPAR surface expression in neurons. Fine modulation of AMPAR membrane trafficking is fundamental in normal synaptic activity and in plasticity processes and CPT1C is therefore a putative candidate to regulate neuronal AMPAR physiology.
authors.affiliation: Laboratori de Neurobiologia, Area de Neurobiologia Cellular i Molecular, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL L'Hospitalet de Llobregat, Spain ; Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona L'Hospitalet de Llobregat, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gratacòs-Batlle
authors.affiliation: Laboratori de Neurobiologia, Area de Neurobiologia Cellular i Molecular, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL L'Hospitalet de Llobregat, Spain ; Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona L'Hospitalet de Llobregat, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Yefimenko
authors.affiliation: Laboratori de Neurobiologia, Area de Neurobiologia Cellular i Molecular, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL L'Hospitalet de Llobregat, Spain ; Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona L'Hospitalet de Llobregat, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Cascos-García
authors.affiliation: Laboratori de Neurobiologia, Area de Neurobiologia Cellular i Molecular, Institut d'Investigació Biomèdica de Bellvitge-IDIBELL L'Hospitalet de Llobregat, Spain ; Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona L'Hospitalet de Llobregat, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Soto
keywords: AMPAR trafficking; CPT1C; GluA1; cortical neurons; electrophysiological recordings; glutamate receptors; palmitoylation; surface expression