PMID- 32437540 OWN - NLM STAT- MEDLINE DCOM- 20210415 LR - 20210415 IS - 1537-1719 (Electronic) IS - 0737-4038 (Linking) VI - 37 IP - 10 DP - 2020 Oct 1 TI - Chaperone-Mediated Autophagy in the Light of Evolution: Insight from Fish. PG - 2887-2899 LID - 10.1093/molbev/msaa127 [doi] AB - Chaperone-mediated autophagy (CMA) is a major pathway of lysosomal proteolysis recognized as a key player of the control of numerous cellular functions, and whose defects have been associated with several human pathologies. To date, this cellular function is presumed to be restricted to mammals and birds, due to the absence of an identifiable lysosome-associated membrane protein 2A (LAMP2A), a limiting and essential protein for CMA, in nontetrapod species. However, the recent identification of expressed sequences displaying high homology with mammalian LAMP2A in several fish species challenges that view and suggests that CMA likely appeared earlier during evolution than initially thought. In the present study, we provide a comprehensive picture of the evolutionary history of the LAMP2 gene in vertebrates and demonstrate that LAMP2 indeed appeared at the root of the vertebrate lineage. Using a fibroblast cell line from medaka fish (Oryzias latipes), we further show that the splice variant lamp2a controls, upon long-term starvation, the lysosomal accumulation of a fluorescent reporter commonly used to track CMA in mammalian cells. Finally, to address the physiological role of Lamp2a in fish, we generated knockout medaka for that specific splice variant, and found that these deficient fish exhibit severe alterations in carbohydrate and fat metabolisms, in consistency with existing data in mice deficient for CMA in liver. Altogether, our data provide the first evidence for a CMA-like pathway in fish and bring new perspectives on the use of complementary genetic models, such as zebrafish or medaka, for studying CMA in an evolutionary perspective. CI - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Lescat, Laury AU - Lescat L AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. FAU - Veron, Vincent AU - Veron V AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. FAU - Mourot, Brigitte AU - Mourot B AD - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, Rennes, France. FAU - Peron, Sandrine AU - Peron S AD - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, Rennes, France. FAU - Chenais, Nathalie AU - Chenais N AD - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, Rennes, France. FAU - Dias, Karine AU - Dias K AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. FAU - Riera-Heredia, Natalia AU - Riera-Heredia N AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. FAU - Beaumatin, Florian AU - Beaumatin F AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. FAU - Pinel, Karine AU - Pinel K AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. FAU - Priault, Muriel AU - Priault M AD - CNRS, IBGC, UMR5095, Bordeaux, France. AD - IBGC, UMR5095, Universite de Bordeaux, Bordeaux, France. FAU - Panserat, Stephane AU - Panserat S AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. FAU - Salin, Benedicte AU - Salin B AD - CNRS, IBGC, UMR5095, Bordeaux, France. AD - IBGC, UMR5095, Universite de Bordeaux, Bordeaux, France. AD - Service Commun de Microscopie, Universite de Bordeaux, Bordeaux, France. FAU - Guiguen, Yann AU - Guiguen Y AD - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, Rennes, France. FAU - Bobe, Julien AU - Bobe J AD - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, Rennes, France. FAU - Herpin, Amaury AU - Herpin A AD - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, Rennes, France. AD - State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan, P.R. China. FAU - Seiliez, Iban AU - Seiliez I AD - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition Metabolisme et Aquaculture, F-64310 Saint-Pee-sur-Nivelle, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Biol Evol JT - Molecular biology and evolution JID - 8501455 RN - 0 (Lysosomal-Associated Membrane Protein 2) SB - IM CIN - Autophagy. 2020 Oct;16(10):1918-1920. PMID: 32772633 MH - Animals MH - Carbohydrate Metabolism MH - Cell Line MH - *Chaperone-Mediated Autophagy MH - *Evolution, Molecular MH - Exons MH - Fibroblasts/physiology MH - Humans MH - Lipid Metabolism MH - Lysosomal-Associated Membrane Protein 2/*genetics/metabolism MH - Mice MH - Oryzias/*genetics/metabolism OTO - NOTNLM OT - CMA OT - Lamp2a OT - autophagy OT - chaperone-mediated autophagy OT - evolution OT - fish OT - medaka EDAT- 2020/05/22 06:00 MHDA- 2021/04/16 06:00 CRDT- 2020/05/22 06:00 PHST- 2020/05/22 06:00 [pubmed] PHST- 2021/04/16 06:00 [medline] PHST- 2020/05/22 06:00 [entrez] AID - 5841670 [pii] AID - 10.1093/molbev/msaa127 [doi] PST - ppublish SO - Mol Biol Evol. 2020 Oct 1;37(10):2887-2899. doi: 10.1093/molbev/msaa127.