{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:07:25Z","timestamp":1789153645183,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012301","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2024YFA1803401"],"award-info":[{"award-number":["2024YFA1803401"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2021YFA0805802"],"award-info":[{"award-number":["2021YFA0805802"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","award":["2024YFA1306100"],"award-info":[{"award-number":["2024YFA1306100"]}],"id":[{"id":"10.13039\/501100012165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32170790"],"award-info":[{"award-number":["32170790"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32321004"],"award-info":[{"award-number":["32321004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Disruption of endoplasmic reticulum (ER) homeostasis activates the unfolded protein response (UPR) to restore proteostasis. Although defects in the secretory machinery can induce ER stress, whether specific trafficking components actively couple cargo handling to UPR signaling remains unclear. Here, using\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    genetics, imaging, and biochemical assays, we show that neuronal overexpression of the gap junction protein UNC-9 cell-autonomously activates the IRE-1-XBP-1 branch of the ER UPR. Loss of the early secretory pathway proteins ERGI-2 or ERGI-3 suppresses this response and disrupts UNC-9 localization, revealing functions for these proteins that extend beyond cargo trafficking. ERGI-2 and ERGI-3 interact with both UNC-9 and the ER chaperone HSP-4\/BiP, suggesting that they couple the handling of excessive UNC-9 to UPR activation. This requirement is cargo-selective: ERGI-2 and ERGI-3 are dispensable for UPR activation induced by overexpression of another innexin, UNC-7, or unrelated proteins. Moreover, activation of the IRE-1-XBP-1 pathway reduces abnormal UNC-9 accumulation in\n                    <jats:italic>ergi-2<\/jats:italic>\n                    and\n                    <jats:italic>ergi-3<\/jats:italic>\n                    mutants. Together, our findings identify ER-to-Golgi trafficking proteins as cargo-selective regulators that link secretory-pathway demand to adaptive UPR.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012301","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:46:20Z","timestamp":1788889580000},"page":"e1012301","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["ER-to-Golgi transport machinery promotes the excessive cargo-triggered unfolded protein response in C. elegans"],"prefix":"10.1371","volume":"22","author":[{"given":"Liying","family":"Guan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Metabolism and Regulation in Complex Organization, Taikang Center for Life and Medical Sciences, School of Basic Medical Sciences, Wuhan University","place":["Wuhan, China"]},{"name":"Institute of Genetics and Developmental Biology, Chinese Academy 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Developmental Biology, Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2653-8293","authenticated-orcid":true,"given":"Xun","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Metabolism and Regulation in Complex Organization, Taikang Center for Life and Medical Sciences, School of Basic Medical Sciences, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0576-6024","authenticated-orcid":true,"given":"Mei","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Metabolism and Regulation in Complex Organization, Taikang Center for Life and Medical Sciences, School 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