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Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils
Abstract
Despite having a high degree of sequence similarity, the Rho guanosine triphosphatases Rac1 and Rac2 regulate distinct functions in neutrophils. Here we demonstrate that the unique Rac2 localization and functions in neutrophils are regulated by two separate C-terminal motifs, the hypervariable domain and aspartic acid 150, one of which has not previously been linked to the function of Rho GTPases. In addition, we show an unexpected dependence of Rac1 localization on Rac2 activity in these same cells, demonstrating a degree of crosstalk between two closely related Rho GTPases. Thus, we have defined specific sequences in Rac that specify subcellular localization and determine the specificity of Rac2 in neutrophil chemotaxis and superoxide generation.
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“Subcellular localization of Rac proteins has been shown to be critical for signal transduction and cellular functions in other cells.13,19”
From Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells (2008) · cites this paper as [19]
In the citing paper
“Diversity in the polybasic domains appears to confer the unique function and localization of the Rho GTPases.19”
From Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells (2008) · cites this paper as [19]
In the citing paper
“Both RhoH (Figure 6A) and Rac1 have a conserved polybasic domain and a CAAX prenylation site in their C termini.7,19,30”
From Cross-talk between RhoH and Rac1 in regulation of actin cytoskeleton and chemotaxis of hematopoietic progenitor cells (2008) · cites this paper as [19]
In the citing paper
“Rac1 and Rac2 also regulate distinct aspects of cytoskeletal reorganization (Filippi et al., 2004).”
From Rac Guanosine Triphosphatases Represent Integrating Molecular Therapeutic Targets for BCR-ABL-Induced Myeloproliferative Disease (2007) · cites this paper as Filippi et al., 2004
In the citing paper
“Murine knock-out models have showed that despite the very high amino acid sequence homology, RAC1 and RAC2 have non-redundant functions in hematopoietic cells, which could be explained at least in part by the differences in the C-termini of the two proteins leading to their distinct subcellular distribution in murine neutrophils [47].”
From Mitochondrial Dysfunction in Human Leukemic Stem/Progenitor Cells upon Loss of RAC2 (2015) · cites this paper as [47]
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Metadata
- Authors
- Filippi, M.-D., Harris, C. E., Meller, J., Gu, Y., Zheng, Y., & Williams, D. A.
- Venue
- Nature Immunology
- Published
- 2004-05-30
- Volume
- 5
- Issue
- 7
- Pages
- 744-751
- ISSN
- 1529-2908
- 1529-2916
- Cited by
- 110
- References
- 0
- Language
- en
- Licence
- www.springer.com/tdm (tdm)
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- Filippi, M.-D., Harris, C. E., Meller, J., Gu, Y., Zheng, Y., & Williams, D. A. (2004). Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils. Nature Immunology. https://doi.org/10.1038/ni1081
