start-ver=1.4 cd-journal=joma no-vol=23 cd-vols= no-issue=10 article-no= start-page=101648 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20201023 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons en-subtitle= kn-subtitle= en-abstract= kn-abstract=Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER. en-copyright= kn-copyright= en-aut-name=MiyataTakashi en-aut-sei=Miyata en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HagiwaraDaisuke en-aut-sei=Hagiwara en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HodaiYuichi en-aut-sei=Hodai en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MiwataTsutomu en-aut-sei=Miwata en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawaguchiYohei en-aut-sei=Kawaguchi en-aut-mei=Yohei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurimotoJunki en-aut-sei=Kurimoto en-aut-mei=Junki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OzakiHajime en-aut-sei=Ozaki en-aut-mei=Hajime kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MitsumotoKazuki en-aut-sei=Mitsumoto en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=TakagiHiroshi en-aut-sei=Takagi en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SugaHidetaka en-aut-sei=Suga en-aut-mei=Hidetaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KobayashiTomoko en-aut-sei=Kobayashi en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=SugiyamaMariko en-aut-sei=Sugiyama en-aut-mei=Mariko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OnoueTakeshi en-aut-sei=Onoue en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ItoYoshihiro en-aut-sei=Ito en-aut-mei=Yoshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=IwamaShintaro en-aut-sei=Iwama en-aut-mei=Shintaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=BannoRyoichi en-aut-sei=Banno en-aut-mei=Ryoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=MatsumotoMami en-aut-sei=Matsumoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=KawakamiNatsuko en-aut-sei=Kawakami en-aut-mei=Natsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=OhnoNobuhiko en-aut-sei=Ohno en-aut-mei=Nobuhiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=SakamotoHirotaka en-aut-sei=Sakamoto en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=ArimaHiroshi en-aut-sei=Arima en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=2 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=3 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=5 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=6 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=7 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=8 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=10 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=11 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=14 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=15 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=16 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= affil-num=17 en-affil=Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences kn-affil= affil-num=18 en-affil=Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences kn-affil= affil-num=19 en-affil=Department of Anatomy, Division of Histology and Cell Biology, Jichi Medical University, School of Medicine kn-affil= affil-num=20 en-affil=Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=21 en-affil=Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine kn-affil= END