Expression and function of Noxo1γ, an alternative splicing form of the NADPH oxidase organizer 1

Ryu Takeya, Masahiko Taura, Tomoko Yamasaki, Seiji Naito, Hideki Sumimoto

Research output: Contribution to journalArticle

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Abstract

Activation of the superoxide-producing NADPH oxidase Nox1 requires both the organizer protein Noxo1 and the activator protein Noxa1. Here we describe an alternative splicing form of Noxo1, Noxo1γ, which is expressed in the testis and fetal brain. The Noxo1γ protein contains an additional five amino acids in the N-terminal PX domain, a phosphoinositide-binding module; the domain plays an essential role in supporting superoxide production by NADPH oxidase (Nox) family oxidases including Nox1, gp91phox/Nox2, and Nox3, as shown in this study. The PX domain isolated from Noxo1γ shows a lower affinity for phosphoinositides than that from the classical splicing form Noxo1β. Consistent with this, in resting cells, Noxo1γ is poorly localized to the membrane, and thus less effective in activating Nox1 than Noxo1β, which is constitutively present at the membrane. On the other hand, cell stimulation with phorbol 12-myristate 13-acetate (PMA), an activator of Nox1-3, facilitates membrane translocation of Noxo1γ; as a result, Noxo1γ is equivalent to Noxo1β in Nox1 activation in PMA-stimulated cells. The effect of the five-amino-acid insertion in the Noxo1 PX domain appears to depend on the type of Nox; in activation of gp91phox/Nox2, Noxo1γ is less active than Noxo1β even in the presence of PMA, whereas Noxo1γ and Noxo1β support the superoxide-producing activity of Nox3 to the same extent in a manner independent of cell stimulation.

Original languageEnglish
Pages (from-to)3663-3677
Number of pages15
JournalFEBS Journal
Volume273
Issue number16
DOIs
Publication statusPublished - Aug 1 2006

Fingerprint

NADPH Oxidase
Alternative Splicing
Superoxides
Acetates
Chemical activation
Phosphatidylinositols
Membranes
Amino Acids
Proteins
Brain
Oxidoreductases
Testis
phorbol-12-myristate
NADPH oxidase 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Expression and function of Noxo1γ, an alternative splicing form of the NADPH oxidase organizer 1. / Takeya, Ryu; Taura, Masahiko; Yamasaki, Tomoko; Naito, Seiji; Sumimoto, Hideki.

In: FEBS Journal, Vol. 273, No. 16, 01.08.2006, p. 3663-3677.

Research output: Contribution to journalArticle

Takeya, Ryu ; Taura, Masahiko ; Yamasaki, Tomoko ; Naito, Seiji ; Sumimoto, Hideki. / Expression and function of Noxo1γ, an alternative splicing form of the NADPH oxidase organizer 1. In: FEBS Journal. 2006 ; Vol. 273, No. 16. pp. 3663-3677.
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