4did

Structural highlights

Function

[CDC42_HUMAN] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.^{[1] [2] [3]} [SOPB_SALTY] Converts phosphatidylinositol 3,4,5-trisphosphate (PtdIns 3,4,5-P3) to PtdIns 3-P and prevents the transition of PtdIns 3-P to PtdIns 3,5-P2. It is one of the known effectors injected by Salmonella into the host cell and is required for invasion and for an efficient generation and maintenance of Salmonella-containing vacuole (SVC). Alteration of the phosphoinositide composition of the plasma membrane causes membrane ruffling and actin cytoskeleton rearrangements. The persistence of PtdIns 3-P diverts the SCV from the endocytic pathway resulting in enlarged vesicles, which are essential to create a favorable environment where Salmonella can replicate and avoid immune defenses of the host cell.^{[4] [5] [6] [7]}

See Also

• GTP-binding protein

References

1. ↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
2. ↑ Oceguera-Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, Haraguchi T, Narumiya S. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005 Jan 17;168(2):221-32. Epub 2005 Jan 10. PMID:15642749 doi:10.1083/jcb.200408085
3. ↑ Modzelewska K, Newman LP, Desai R, Keely PJ. Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. PMID:17038317 doi:10.1074/jbc.M604342200
4. ↑ Mirold S, Ehrbar K, Weissmuller A, Prager R, Tschape H, Russmann H, Hardt WD. Salmonella host cell invasion emerged by acquisition of a mosaic of separate genetic elements, including Salmonella pathogenicity island 1 (SPI1), SPI5, and sopE2. J Bacteriol. 2001 Apr;183(7):2348-58. PMID:11244077 doi:http://dx.doi.org/10.1128/JB.183.7.2348-2358.2001
5. ↑ Zhou D, Chen LM, Hernandez L, Shears SB, Galan JE. A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol Microbiol. 2001 Jan;39(2):248-59. PMID:11136447
6. ↑ Terebiznik MR, Vieira OV, Marcus SL, Slade A, Yip CM, Trimble WS, Meyer T, Finlay BB, Grinstein S. Elimination of host cell PtdIns(4,5)P(2) by bacterial SigD promotes membrane fission during invasion by Salmonella. Nat Cell Biol. 2002 Oct;4(10):766-73. PMID:12360287 doi:http://dx.doi.org/10.1038/ncb854
7. ↑ Hernandez LD, Hueffer K, Wenk MR, Galan JE. Salmonella modulates vesicular traffic by altering phosphoinositide metabolism. Science. 2004 Jun 18;304(5678):1805-7. PMID:15205533 doi:http://dx.doi.org/10.1126/science.1098188
8. ↑ Burkinshaw B, Strynadka NC. Structure of Salmonella Effector Protein SopB N-terminal domain in complex with Host Rho GTPase Cdc42. J Biol Chem. 2012 Feb 23. PMID:22362774 doi:10.1074/jbc.M111.331330