Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2
- PMID: 17302440
- DOI: 10.1021/bi062152y
Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2
Abstract
The Wiskott-Aldrich syndrome protein (WASP) and neural WASP (N-WASP) are key players in regulating actin cytoskeleton via the Arp2/3 complex. It has been widely reported that the WASP proteins are activated by Rho family small GTPase Cdc42 and that Rac1 acts through SCAR/WAVE proteins. However, a systematic study of the specificity of different GTPases for different Arp2/3 activators has not been conducted. In this study, we have expressed, purified, and characterized completely soluble, highly active, and autoinhibited full-length human WASP and N-WASP from mammalian cells. We show a novel N-WASP activation by Rho family small GTPase Rac1. This GTPase exclusively stimulates N-WASP and has no effects on WASP. Rac1 is a significantly more potent N-WASP activator than Cdc42. In contrast, Cdc42 is a more effective activator of WASP than N-WASP. Lipid vesicles containing PIP2 significantly improve actin nucleation by the Arp2/3 complex and N-WASP in the presence of Rac1 or Cdc42. PIP2 vesicles have no effect on WASP activity alone. Moreover, the inhibition of WASP-stimulated actin nucleation in the presence of Cdc42 and PIP2 vesicles has been observed. We found that adaptor proteins Nck1 or Nck2 are the most potent WASP and N-WASP activators with distinct effects on the WASP family members. Our in vitro data demonstrates differential regulation of full-length WASP and N-WASP by cellular activators that highlights fundamental differences of response at the protein-protein level.
Similar articles
-
Involvement of Rho GTPases and their effectors in the secretory process of PC12 cells.Exp Cell Res. 2002 Feb 15;273(2):119-26. doi: 10.1006/excr.2001.5432. Exp Cell Res. 2002. PMID: 11822867
-
Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck.Nature. 2002 Aug 15;418(6899):790-3. doi: 10.1038/nature00859. Nature. 2002. PMID: 12181570
-
Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes.Nat Cell Biol. 2005 Oct;7(10):969-76. doi: 10.1038/ncb1304. Epub 2005 Sep 11. Nat Cell Biol. 2005. PMID: 16155590
-
WASp in immune-system organization and function.Nat Rev Immunol. 2002 Sep;2(9):635-46. doi: 10.1038/nri884. Nat Rev Immunol. 2002. PMID: 12209132 Review.
-
Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation.Microsc Res Tech. 1999 Oct 15;47(2):107-13. doi: 10.1002/(SICI)1097-0029(19991015)47:2<107::AID-JEMT3>3.0.CO;2-H. Microsc Res Tech. 1999. PMID: 10523789 Review.
Cited by
-
Enteropathogenic E. coli relies on collaboration between the formin mDia1 and the Arp2/3 complex for actin pedestal biogenesis and maintenance.PLoS Pathog. 2018 Dec 14;14(12):e1007485. doi: 10.1371/journal.ppat.1007485. eCollection 2018 Dec. PLoS Pathog. 2018. PMID: 30550556 Free PMC article.
-
Cytoskeletal control of B cell responses to antigens.Nat Rev Immunol. 2017 Oct;17(10):621-634. doi: 10.1038/nri.2017.67. Epub 2017 Jul 10. Nat Rev Immunol. 2017. PMID: 28690317 Review.
-
Molecular difference between WASP and N-WASP critical for chemotaxis of T-cells towards SDF-1α.Sci Rep. 2015 Oct 14;5:15031. doi: 10.1038/srep15031. Sci Rep. 2015. PMID: 26463123 Free PMC article.
-
Physical mechanisms of signal integration by WASP family proteins.Annu Rev Biochem. 2010;79:707-35. doi: 10.1146/annurev.biochem.77.060407.135452. Annu Rev Biochem. 2010. PMID: 20533885 Free PMC article. Review.
-
Further insights into cortactin conformational regulation.Bioarchitecture. 2011 Jan;1(1):21-23. doi: 10.4161/bioa.1.1.14631. Bioarchitecture. 2011. PMID: 21866257 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
