Differential cell surface recruitment of the superoxide‐producing NADPH oxidases Nox1, Nox2 and Nox5: The role of the small GTPase Sar1

Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII‐coated vesicles en route to the cell surface. Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide‐producing NADPH oxidase, is transported to the cell...

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Published in:Genes to cells : devoted to molecular & cellular mechanisms 2018-06, Vol.23 (6), p.480-493
Main Authors: Kiyohara, Takuya, Miyano, Kei, Kamakura, Sachiko, Hayase, Junya, Chishiki, Kanako, Kohda, Akira, Sumimoto, Hideki
Format: Article
Language:English
Subjects:
Cell surface
Coated vesicles
CYBB protein
Defective mutant
Endoplasmic reticulum
Glycoproteins
Glycosylation
Golgi apparatus
Guanosine triphosphatases
Guanosine triphosphate
Mannose
NAD(P)H oxidase
NADPH oxidase
Nox1
Nox2
Nox5
N‐linked glycosylation
plasma membrane
protein targeting
reactive oxygen species
Sar1
SNAP receptors
Superoxide
Syntaxin
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Summary:Transmembrane glycoproteins, synthesized at the endoplasmic reticulum (ER), generally reach the Golgi apparatus in COPII‐coated vesicles en route to the cell surface. Here, we show that the bona fide nonglycoprotein Nox5, a transmembrane superoxide‐producing NADPH oxidase, is transported to the cell surface in a manner resistant to co‐expression of Sar1 (H79G), a GTP‐fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the ER. In contrast, Sar1 (H79G) effectively inhibits ER‐to‐Golgi transport of glycoproteins including the Nox5‐related oxidase Nox2. The trafficking of Nox2, but not that of Nox5, is highly sensitive to over‐expression of syntaxin 5 (Stx5), a t‐SNARE required for COPII ER‐to‐Golgi transport. Thus, Nox2 and Nox5 mainly traffic via the Sar1/Stx5‐dependent and ‐independent pathways, respectively. Both participate in Nox1 trafficking, as Nox1 advances to the cell surface in two differentially N‐glycosylated forms, one complex and one high mannose, in a Sar1/Stx5‐dependent and ‐independent manner, respectively. Nox2 and Nox5 also can use both pathways: a glycosylation‐defective mutant Nox2 is weakly recruited to the plasma membrane in a less Sar1‐dependent manner; N‐glycosylated Nox5 mutants reach the cell surface in part as the complex form Sar1‐dependently, albeit mainly as the high‐mannose form in a Sar1‐independent manner. The nonglycoprotein Nox5, a transmembrane superoxide‐producing NADPH oxidase, is mainly transported from the ER to the cell surface via an unconventional pathway, which is independent of the small GTPase Sar1 and the t‐SNARE syntaxin 5 (Stx5). The glycoprotein Nox2 traffics conventionally, whereas Nox1, another glycosylated oxidase, uses both the Sar1/Stx‐dependent and Sar1/Stx‐independent pathways. Thus, Nox1, Nox2 and Nox5 are differentially recruited to the plasma membrane.
ISSN:1356-9597
1365-2443
DOI:10.1111/gtc.12590