PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells
- PMID: 18086913
- PMCID: PMC2140022
- DOI: 10.1083/jcb.200706167
PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells
Abstract
Chemoattractants such as formyl-Met-Leu-Phe (fMLP) induce neutrophils to polarize by triggering divergent pathways that promote formation of a protrusive front and contracting back and sides. RhoA, a Rho GTPase, stimulates assembly of actomyosin contractile complexes at the sides and back. We show here, in differentiated HL60 cells, that PDZRhoGEF (PRG), a guanine nucleotide exchange factor (GEF) for RhoA, mediates RhoA-dependent responses and determines their spatial distribution. As with RNAi knock-down of PRG, a GEF-deleted PRG mutant blocks fMLP-dependent RhoA activation and causes neutrophils to exhibit multiple fronts and long tails. Similarly, inhibition of RhoA, a Rho-dependent protein kinase (ROCK), or myosin II produces the same morphologies. PRG inhibition reduces or mislocalizes monophosphorylated myosin light chains in fMLP-stimulated cells, and myosin II ATPase inhibition reciprocally disrupts normal localization of PRG. We propose a cooperative reinforcing mechanism at the back of cells, in which PRG, RhoA, ROCK, myosin II, and actomyosin spatially cooperate to consolidate attractant-induced contractility and ensure robust cell polarity.
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References
-
- Arthur, W.T., N.K. Noren, and K. Burridge. 2002. Regulation of Rho Family GTPases by Cell-Cell and Cell-Matrix Adhesion. Biol. Res. 35:239–246. - PubMed
-
- Barac, A., J. Basile, J. Vazquez-Prado, Y. Gao, Y. Zheng, and J.S. Gutkind. 2004. Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor. J. Biol. Chem. 279:6182–6189. - PubMed
-
- Basile, J.R., A. Barac, T. Zhu, K.L. Guan, and J.S. Gutkind. 2004. Class IV semaphorins promote angiogenesis by stimulating Rho-initiated pathways through plexin-B. Cancer Res. 64:5212–5224. - PubMed
-
- Driessens, M.H., C. Olivo, K. Nagata, M. Inagaki, and J.G. Collard. 2002. B plexins activate Rho through PDZ-RhoGEF. FEBS Lett. 529:168–172. - PubMed
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