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Signal sequence-triage is activated by translocon obstruction sensed by an ER stress sensor IRE1α.
Sogawa, Ashuei; Komori, Ryota; Yanagitani, Kota; Ohfurudono, Miku; Tsuru, Akio; Kadoi, Koji; Kimata, Yukio; Yoshida, Hiderou; Kohno, Kenji.
Afiliação
  • Sogawa A; Laboratory of Molecular and Cell Genetics, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST).
  • Komori R; Osaka International Cancer Institute (OICI).
  • Yanagitani K; Institute for Research Initiatives, Nara Institute of Science and Technology (NAIST).
  • Ohfurudono M; Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST).
  • Tsuru A; Department of Biochemistry and Molecular Biology, Graduate School of Science, University of Hyogo.
  • Kadoi K; Institute for Research Initiatives, Nara Institute of Science and Technology (NAIST).
  • Kimata Y; Ubiquitin Biology Laboratory, Graduate School of Frontier Biosciences, Osaka University.
  • Yoshida H; Laboratory of Molecular and Cell Genetics, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST).
  • Kohno K; Institute for Research Initiatives, Nara Institute of Science and Technology (NAIST).
Cell Struct Funct ; 48(2): 211-221, 2023 Nov 03.
Article em En | MEDLINE | ID: mdl-37766570
Secretory pathway proteins are cotranslationally translocated into the endoplasmic reticulum (ER) of metazoan cells through the protein channel, translocon. Given that there are far fewer translocons than ribosomes in a cell, it is essential that secretory protein-translating ribosomes only occupy translocons transiently. Therefore, if translocons are obstructed by ribosomes stalled or slowed in translational elongation, it possibly results in deleterious consequences to cellular function. Hence, we investigated how translocon clogging by stalled ribosomes affects mammalian cells. First, we constructed ER-destined translational arrest proteins (ER-TAP) as an artificial protein that clogged the translocon in the ER membrane. Here, we show that the translocon clogging by ER-TAP expression activates triage of signal sequences (SS) in which secretory pathway proteins harboring highly efficient SS are preferentially translocated into the ER lumen. Interestingly, the translocon obstructed status specifically activates inositol requiring enzyme 1α (IRE1α) but not protein kinase R-like ER kinase (PERK). Given that the IRE1α-XBP1 pathway mainly induces the translocon components, our discovery implies that lowered availability of translocon activates IRE1α, which induces translocon itself. This results in rebalance between protein influx into the ER and the cellular translocation capacity.Key words: endoplasmic reticulum, translocation capacity, translocon clogging, IRE1, signal sequence.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / Endorribonucleases Limite: Animals Idioma: En Revista: Cell Struct Funct Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Serina-Treonina Quinases / Endorribonucleases Limite: Animals Idioma: En Revista: Cell Struct Funct Ano de publicação: 2023 Tipo de documento: Article