title: Expanded polyglutamine embedded in the endoplasmic reticulum causes membrane distortion and coincides with Bax insertion.
abstract: The endoplasmic reticulum (ER) is important in various cellular functions, such as secretary and membrane protein biosynthesis, lipid synthesis, and calcium storage. ER stress, including membrane distortion, is associated with many diseases such as Huntington's disease. In particular, nuclear envelope distortion is related to neuronal cell death associated with polyglutamine. However, the mechanism by which polyglutamine causes ER membrane distortion remains unclear. We used electron microscopy, fluorescence protease protection assay, and alkaline treatment to analyze the localization of polyglutamine in cells. We characterized polyglutamine embedded in the ER membrane and noted an effect on morphology, including the dilation of ER luminal space and elongation of ER-mitochondria contact sites, in addition to the distortion of the nuclear envelope. The polyglutamine embedded in the ER membrane was observed at the same time as Bax insertion. These results demonstrated that the ER membrane may be a target of polyglutamine, which triggers cell death through Bax.
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Shimo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Miao-Xing
authors.initials: MX
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hayakawa
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Saiful
authors.initials: S
authors.lastname: Islam
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.lastname: Tana
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Anatomy, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Huayue
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: tnakagaw@gifu-u.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakagawa
mesh_terms: D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008560:Membrane Fluidity / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494827:Bax protein, mouse; D010455:Peptides; D051028:bcl-2-Associated X Protein; C097188:polyglutamine
keywords: Apoptosis; Endoplasmic reticulum; Membrane; Polyglutamine