iScience (Oct 2020)
Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons
- Takashi Miyata,
- Daisuke Hagiwara,
- Yuichi Hodai,
- Tsutomu Miwata,
- Yohei Kawaguchi,
- Junki Kurimoto,
- Hajime Ozaki,
- Kazuki Mitsumoto,
- Hiroshi Takagi,
- Hidetaka Suga,
- Tomoko Kobayashi,
- Mariko Sugiyama,
- Takeshi Onoue,
- Yoshihiro Ito,
- Shintaro Iwama,
- Ryoichi Banno,
- Mami Matsumoto,
- Natsuko Kawakami,
- Nobuhiko Ohno,
- Hirotaka Sakamoto,
- Hiroshi Arima
Affiliations
- Takashi Miyata
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Daisuke Hagiwara
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Corresponding author
- Yuichi Hodai
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Tsutomu Miwata
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Yohei Kawaguchi
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Junki Kurimoto
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Hajime Ozaki
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Kazuki Mitsumoto
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Hiroshi Takagi
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Hidetaka Suga
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Tomoko Kobayashi
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Mariko Sugiyama
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Takeshi Onoue
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Yoshihiro Ito
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Shintaro Iwama
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
- Ryoichi Banno
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya 464-8601, Japan
- Mami Matsumoto
- Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences, Okazaki 444-8787, Japan
- Natsuko Kawakami
- Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University, Setouchi 701-4303, Japan
- Nobuhiko Ohno
- Department of Anatomy, Division of Histology and Cell Biology, Jichi Medical University, School of Medicine, Shimotsuke 329-0498, Japan; Division of Ultrastructural Research, National Institute for Physiological Sciences, Okazaki 444-8787, Japan
- Hirotaka Sakamoto
- Ushimado Marine Institute, Graduate School of Natural Science and Technology, Okayama University, Setouchi 701-4303, Japan
- Hiroshi Arima
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Corresponding author
- Journal volume & issue
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Vol. 23,
no. 10
p. 101648
Abstract
Summary: 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.
