title: Specific distribution of the autophagic protein GABARAPL1/GEC1 in the developing and adult mouse brain and identification of neuronal populations expressing GABARAPL1/GEC1.
abstract: Macroautophagy is a highly conserved cellular degradation process, regulated by autophagy-related (atg) factors, in which a double membrane autophagosome engulfs cytoplasmic components to target them for degradation. In yeast, the Atg8 protein is indispensable for autophagosome formation. In mammals, this is complicated by the presence of six Atg8 homologues grouped into the GABARAP and MAP1LC3 subfamilies. Although these proteins share a high similarity, their transcript expression, regulation and protein interactions differ, suggesting they may display individual properties and specific functions. GABARAPL1/GEC1 is a member of the GABARAP subfamily and its mRNA is the most highly expressed Atg8 homologue in the central nervous system. Consequently, we performed an in depth study of GABARAPL1 distribution in the developing and adult murine brain. Our results show that GABARAPL1 brain expression is visible as early as embryonic day 11 and progressively increases to a maximum level in the adult. Immunohistochemical staining was detected in both fibers and immature neurons in embryos but was restrained to neurons in adult tissue. By E17, intense punctate-like structures were visible and these accumulated in cortical primary neurons treated with the autophagosome/lysosome fusion inhibitor Bafilomycin A1 (Baf A1), suggesting that they represent autophagosomes. Finally, GABARAPL1 expression was particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta, a region affected in Parkinson's disease. Our study of cerebral GABARAPL1 protein expression provides insight into its role in the development and homeostasis of the mouse brain.
authors.affiliation: Université de Franche-Comté, Laboratoire de Biochimie, EA3922 Estrogènes, Expression Génique et Pathologies du Système Nerveux Central, SFR IBCT FED 4234, U.F.R. Sciences et Techniques, Besançon, Doubs, France.
authors.forename: Jaclyn Nicole
authors.initials: JN
authors.lastname: Le Grand
authors.forename: Karine
authors.initials: K
authors.lastname: Bon
authors.forename: Annick
authors.initials: A
authors.lastname: Fraichard
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Michèle
authors.initials: M
authors.lastname: Jouvenot
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Risold
authors.forename: Michaël
authors.initials: M
authors.lastname: Boyer-Guittaut
authors.forename: Régis
authors.initials: R
authors.lastname: Delage-Mourroux
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001343:Autophagy; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C480859:Gabarapl1 protein, mouse; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger