Title : N-Linked glycosylation of the superoxide-producing NADPH oxidase
Nox1
Abstract :
- Nox1 is a membrane-integrated protein that belongs to the Nox family of superoxide-producing NADPH oxidases
- Here we show that human Nox1 undergoes glycosylation at Asn-162 and Asn-236 in the second and third extracellular loops, respectively
- Simultaneous threonine substitution for these residues completely abrogates the glycosylation, but does not prevent Nox1 from forming a heterodimer with p22 (phox), trafficking to the cell surface, or producing superoxide
- In the absence of p22 (phox), Nox1 is transported to the plasma membrane mainly as a form with high mannose N-glycans, although their conversion into complex N-glycans is induced by expression of p22 (phox)
- These findings indicate that glycosylation and subsequent N-glycan maturation of Nox1 are both dispensable for its cell surface recruitment
- Superoxide production by unglycosylated Nox1 is largely dependent on p22 (phox), which is abrogated by glutamine substitution for Pro-156 in p22 (phox), a mutation leading to a defective interaction with the Nox1-activating protein Noxo1
- Thus p22 (phox) directly contributes to Nox1 activation in a glycosylation-independent manner, besides its significant role in Nox1 glycan maturation