RT Journal Article SR Electronic T1 GABARAPs dysfunction by autophagy deficiency in adolescent brain impairs GABAA receptor trafficking and social behavior JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP eaau8237 DO 10.1126/sciadv.aau8237 VO 5 IS 4 A1 Hui, Kelvin K. A1 Takashima, Noriko A1 Watanabe, Akiko A1 Chater, Thomas E. A1 Matsukawa, Hiroshi A1 Nekooki-Machida, Yoko A1 Nilsson, Per A1 Endo, Ryo A1 Goda, Yukiko A1 Saido, Takaomi C. A1 Yoshikawa, Takeo A1 Tanaka, Motomasa YR 2019 UL http://advances.sciencemag.org/content/5/4/eaau8237.abstract AB Dysfunctional mTOR signaling is associated with the pathogenesis of neurodevelopmental and neuropsychiatric disorders. However, it is unclear what molecular mechanisms and pathogenic mediators are involved and whether mTOR-regulated autophagy continues to be crucial beyond neurodevelopment. Here, we selectively deleted Atg7 in forebrain GABAergic interneurons in adolescent mice and unexpectedly found that these mice showed a set of behavioral deficits similar to Atg7 deletion in forebrain excitatory neurons. By unbiased quantitative proteomic analysis, we identified γ-aminobutyric acid receptor–associated protein-like 2 (GABARAPL2) to differentially form high–molecular weight species in autophagy-deficient brains. Further functional analyses revealed a novel pathogenic mechanism involving the p62-dependent sequestration of GABARAP family proteins, leading to the reduction of surface GABAA receptor levels. Our work demonstrates a novel physiological role for autophagy in regulating GABA signaling beyond postnatal neurodevelopment, providing a potential mechanism for the reduced inhibitory inputs observed in neurodevelopmental and neuropsychiatric disorders with mTOR hyperactivation.