Subcellular localization and function of alternatively spliced Noxo1 isoforms

被引:31
作者
Ueyama, Takehiko
Lekstrom, Kristen
Tsujibe, Satoshi
Saito, Naoaki
Leto, Thomas L.
机构
[1] NIAID, NIH, Mol Def Sect, Lab Host Def, Rockville, MD 20852 USA
[2] Kobe Univ, Mol Pharmacol Lab, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan
关键词
D O I
10.1016/j.freeradbiomed.2006.08.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nox organizer 1 (Noxo1), a p47(phox) homolog, is produced as four isoforms with unique N-terminal PX domains derived by alternative mRNA splicing. We compared the subcellular distribution of these isoforms or their isolated PX domains produced as GFP fusion proteins, as well as their ability to support Nox1 activity in several transfected models. Noxo1 alpha, beta, gamma, and delta show different subcellular localization patterns, determined by their PX domains. In HEK293 cells, Noxo1 beta exhibits prominent plasma membrane binding, Noxo1 gamma shows plasma membrane and nuclear associations, and Noxo1 alpha and 6 localize primarily on intracellular vesicles or cytoplasmic aggregates, but not the plasma membrane. Nox1 activity correlates with Noxo1 plasma membrane binding in HEK293 cells, since Noxo1 beta supports the highest activity and Noxo1 gamma and Noxo1 alpha support moderate or low activities, respectively. In COS-7 cells, where Noxo1 alpha localizes on the plasma membrane, the activities supported by the three isoforms (alpha, beta, and gamma) do not differ significantly. The PX domains of beta and gamma bind the same phospholipids, including phosphatidic acid. These results indicate that the variant PX domains are unique determinants of Noxo1 localization and Nox1 function. Finally, the overexpressed Noxo1 isoforms do not affect p22(phox) localization, although Nox1 is needed to transport p22(phox) to the plasma membrane. Published by Elsevier Inc.
引用
收藏
页码:180 / 190
页数:11
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