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

Takuya Kiyohara, Kei Miyano, Sachiko Kamakura, Junya Hayase, Kanako Chishiki, Akira Kohda, Hideki Sumimoto

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)480-493
Number of pages14
JournalGenes to Cells
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 2018

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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