{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:39:06Z","timestamp":1783463946990,"version":"3.55.0"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K17413"],"award-info":[{"award-number":["JP23K17413"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100022598","name":"Toray Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022598","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Japanese Society of Microscopy Young Researchers Research Grant"},{"name":"Pharmacological Research Foundation"},{"DOI":"10.13039\/501100018732","name":"Ohsumi Frontier Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018732","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Center for Experimental Modeling of Human Disease"},{"name":"Institute for Experimental Animals, Kanazawa University"},{"name":"Center for Biomedical Research and Education, Kanazawa University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The synthesis of the melanin pigment in melanocytes plays a crucial role in protecting the body from ultraviolet radiation. Tyrosinase, a key enzyme in melanogenesis, catalyzes the conversion of tyrosine to melanin in the melanosomes of melanocytes. During melanogenesis, Tyrosinase is abundantly synthesized in the lumen of the endoplasmic reticulum (ER) and subsequently transported from the ER to the melanosomes via the Golgi apparatus. In the present study, we demonstrate that Box B-binding factor 2 human homolog on chromosome 7 (BBF2H7), an ER-resident transmembrane transcription factor that functions as an ER stress sensor, is activated by mild ER stress caused by abundant Tyrosinase synthesis. Activated BBF2H7 enhances COPII-mediated anterograde transport by inducing the expression of Sec23a, which is a COPII component and transcriptional target of BBF2H7. Loss of BBF2H7 attenuates the transport of Tyrosinase, leading to its accumulation in the ER lumen and reduced melanin production. Restoration of BBF2H7 or Sec23a expression in Bbf2h7-deficient melanocytes rescues anterograde transport of Tyrosinase from the ER and melanin pigmentation. Collectively, these findings reveal that the BBF2H7-Sec23a axis is essential for the ER-to-melanosome transport of Tyrosinase and subsequent melanin synthesis. Thus, it may be a prospective therapeutic target for disorders related to melanin pigmentation.<\/jats:p>","DOI":"10.3390\/ijms27010501","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T12:38:56Z","timestamp":1767616736000},"page":"501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Vesicular Transport Mediated by Endoplasmic Reticulum Stress Sensor BBF2H7 Orchestrates Melanin Production During Melanogenesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Giang Huy","family":"Phan","sequence":"first","affiliation":[{"name":"Department of Frontier Science and Interdisciplinary Research, Faculty of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8640, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-6504","authenticated-orcid":false,"given":"Kenshiro","family":"Fujise","sequence":"additional","affiliation":[{"name":"Department of Frontier Science and Interdisciplinary Research, Faculty of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8640, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Imaizumi","sequence":"additional","affiliation":[{"name":"The Osaka Medical Research Foundation for Intractable Diseases, 3-7-11, Minamisumiyoshi, Sumiyoshi-Ku, Osaka 558-0041, Osaka, Japan"},{"name":"Department of Child Development and Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita 565-0871, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2425-3371","authenticated-orcid":false,"given":"Atsushi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Frontier Science and Interdisciplinary Research, Faculty of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa 920-8640, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00281-007-0060-9","article-title":"The skin barrier as an innate immune element","volume":"29","author":"Elias","year":"2007","journal-title":"Semin. 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