The NADPH oxidases DUOX1 and DUOX2 are sorted to the apical plasma membrane in epithelial cells via their respective maturation factors DUOXA1 and DUOXA2.

Autor: Kohda A; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan., Kamakura S; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan., Hayase J; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan., Sumimoto H; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Jazyk: angličtina
Zdroj: Genes to cells : devoted to molecular & cellular mechanisms [Genes Cells] 2024 Oct; Vol. 29 (10), pp. 921-930. Date of Electronic Publication: 2024 Aug 10.
DOI: 10.1111/gtc.13153
Abstrakt: The membrane-integrated NADPH oxidases DUOX1 and DUOX2 are recruited to the apical plasma membrane in epithelial cells to release hydrogen peroxide, thereby playing crucial roles in various functions such as thyroid hormone synthesis and host defense. However, it has remained unknown about the molecular mechanism for apical sorting of DUOX1 and DUOX2. Here we show that DUOX1 and DUOX2 are correctly sorted to the apical membrane via the membrane-spanning DUOX maturation proteins DUOXA1 and DUOXA2, respectively, when co-expressed in MDCK epithelial cells. Impairment of N-glycosylation of DUOXA1 results in mistargeting of DUOX1 to the basolateral membrane. Similar to DUOX1 complexed with the glycosylation-defective DUOXA1, the naturally non-glycosylated oxidase NOX5, which forms a homo-oligomer, is targeted basolaterally. On the other hand, a mutant DUOXA2 deficient in N-glycosylation is less stable than the wild-type protein but still capable of recruiting DUOX2 to the apical membrane, whereas DUOX2 is missorted to the basolateral membrane when paired with DUOXA1. These findings indicate that DUOXA2 is crucial but its N-glycosylation is dispensable for DUOX2 apical recruitment; instead, its C-terminal region seems to be involved. Thus, apical sorting of DUOX1 and DUOX2 is likely regulated in a distinct manner by their respective partners DUOXA1 and DUOXA2.
(© 2024 The Author(s). Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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