{"doi":"10.1083/jcb.201912045","title":"Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking","abstract":"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.","journal":"The Journal of Cell Biology","year":2020,"id":97338,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":444136,"name":"Rut Fadó","orcid":"0000-0002-3293-2342","position":1,"is_corresponding":false},{"id":481395,"name":"José Luís Domínguez‐García","orcid":"0000-0002-0483-995X","position":2,"is_corresponding":false},{"id":481396,"name":"Aina Roig","orcid":"0000-0001-6153-6042","position":3,"is_corresponding":false},{"id":482156,"name":"Moena Kaku","orcid":null,"position":4,"is_corresponding":false},{"id":481397,"name":"Shigeru Chohnan","orcid":"0000-0002-4624-927X","position":5,"is_corresponding":false},{"id":444138,"name":"Montse Solé","orcid":"0000-0003-4240-6562","position":6,"is_corresponding":false},{"id":444139,"name":"Mercedes Unzeta","orcid":"0000-0002-7113-3383","position":7,"is_corresponding":false},{"id":444142,"name":"Alfredo J. Miñano‐Molina","orcid":"0000-0002-7761-5682","position":8,"is_corresponding":false},{"id":444141,"name":"José Rodrı́guez-Álvarez","orcid":"0000-0001-8582-8082","position":9,"is_corresponding":false},{"id":355958,"name":"Eamonn J. Dickson","orcid":"0000-0001-8619-7630","position":10,"is_corresponding":false},{"id":444137,"name":"Núria Casals","orcid":"0000-0002-6719-4300","position":11,"is_corresponding":false},{"id":481394,"name":"Maria Casas","orcid":"0000-0002-5246-8874","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T22:35:34.520494Z","pmid":"32931550","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}