著者

Ashuei Sogawa Ryota Komori Kota Yanagitani Miku Ohfurudono Akio Tsuru Koji Kadoi Yukio Kimata Hiderou Yoshida Kenji Kohno

出版者

Japan Society for Cell Biology

雑誌

Cell Structure and Function (ISSN:03867196)

巻号頁・発行日

pp.23072, (Released:2023-09-28)

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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.Keywords: endoplasmic reticulum, translocation capacity, translocon clogging, IRE1, signal sequence

著者

Kanae Sasaki Ryota Komori Mai Taniguchi Akie Shimaoka Sachiko Midori Mayu Yamamoto Chiho Okuda Ryuya Tanaka Miyu Sakamoto Sadao Wakabayashi Hiderou Yoshida

出版者

Japan Society for Cell Biology

雑誌

Cell Structure and Function (ISSN:03867196)

巻号頁・発行日

pp.18031, (Released:2018-11-28)

被引用文献数

15

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The Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer elements PGSE-A and PGSE-B (the consensus sequences are CCGGGGCGGGGCG and TTTTACAATTGGTC, respectively), which regulates their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway. Key words: Golgi stress, proteoglycan, ER stress, organelle zone, organelle autoregulation