Localizing the ROS Signal

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Science's STKE  20 Dec 2005:
Vol. 2005, Issue 315, pp. tw456
DOI: 10.1126/stke.3152005tw456

Reactive oxygen species (ROS) are short-lived molecules. Thus, localizing the production of these molecules is essential if they are to participate in cell signaling events. Two groups report mechanisms for localized production of ROS by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in migrating endothelial cells (Wu et al.) and in the growing tips of plant root hair cells (Carol et al.). Wu et al. report that in endothelial cells, recruitment of the adaptor TRAF4, which binds the p47phox subunit of NADPH oxidase, to focal adhesion sites through interaction with Hic-5, a focal adhesion site scaffold, allowed the local activation of NADPH oxidase, which biased the focal adhesion site environment toward tyrosine phosphorylation through the oxidative inactivation of the tyrosine phosphatase PTP-PEST, and the activation of redox-sensitive kinases such as Pyk2. Forcing TRAF4 to lipid rafts by addition of a myristoylation site also promoted activation of RhoA guanosine triphosphatase (GTPase), as well as the GTPases Cdc42 and Rac1, which increased the activity of the kinase PAK1, leading to phosphorylation and activation of p47phox, which in turn inactivated PTP-PEST by oxidation. Cells expressing the myristoylated TRAF4 also exhibited extensive membrane ruffling, which was blocked in cells also expressing catalytically inactive versions of the tyrosine kinases Pyk2 or Src. Endothelial cell migration was blocked if the abundance of either TRAF4 or Hic-5 was decreased by RNAi or if ROS accumulation was prevented by the addition of a superoxide dismutase mimetic. Thus, TRAF4 provides a mechanism for localized ROS generation, which contributes to a permissive environment for formation of transient peripheral focal adhesion sites. Trichoblasts of Arabidopsis roots form a single root hair by a process involving polarized growth and localized ROS production. Carol et al. identified a Rho GTPase guanine nucleotide dissociation inhibitor (GDI) encoded by the supercentipede (SCN1) gene that, when inactivated, caused multiple root hairs to form. In wild-type roots, ROS are locally produced by RHD2, the Arabidopsis NADPH oxidase. In the scn1 mutants, ROS was produced at the ectopic root hair cell sites and was more broadly distributed. The rhd2 scn1 double-mutant plants exhibited single root hair growth sites that failed to elongate properly. The Rho GTPase ROP2 was also mislocalized in the scn1 mutant root hair cells to the ectopic hair formation sites. These two articles show that localized Rho GTPase activity combined with localized ROS production contribute to polarized growth and movement in plants and animals.

R. F. Wu, Y. C. Xu, Z. Ma, F. E. Nwariaku, G. A. Sarosi Jr., L. S. Terada, Subcellular targeting of oxidants during endothelial cell migration. J. Cell Biol. 171, 893-904 (2005). [Abstract] [Full Text]

R. J. Carol, S. Takeda, P. Linstead, M. C. Durrant, H. Kakesova, P. Derbyshire, S. Drea, V. Zarsky, L. Dolan, A RhoGDP dissociation inhibitor spatially regulates growth in root hair cells. Nature 438, 1013-1016 (2005). [PubMed]

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