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. 2012 Feb 1;31(3):517-8.
doi: 10.1038/emboj.2011.481. Epub 2012 Feb 1.

Rac1 gets fattier

Frederick D Tsai  1 , Mark R Philips
Affiliations

Rac1 gets fattier

Frederick D Tsai et al. EMBO J. .

Abstract

EMBO J 31 3, 534–551 (2012); published online December 09 2011

Since its description more than two decades ago as a substrate for botulinum C3 exoenzyme (Didsbury et al, 1989), Rac1 has been one of the most studied small GTPases of the Ras superfamily. Interest in Rac1 exploded in 1992 when Ridley and Hall published their seminal work showing that Rac1 regulates the actin cytoskeleton to promote lamellipodia formation (Ridley et al, 1992). Since that report, >4350 studies have been published on Rac1 and seemingly every detail of its regulation and biological function has been dissected, including its post-translational modifications. It therefore comes as somewhat of a surprise when del Pozo and colleagues (Navarro-Lérida et al, 2012) report for the first time in this issue of The EMBO Journal that Rac1 can be palmitoylated and that acylation directs its location in plasma membrane microdomains and modulates its signalling output.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
The Rac1 acylation cycle. Rac1 localizes to the plasma membrane by virtue of its geranylgeranyl modification (shown in brown) and its +6 polybasic region (shown in red) once it has been released from its cytosolic chaperone, RhoGDI. At the plasma membrane, Rac1 is activated by a guanine nucleotide exchange factor (GEF) and also undergoes palmitoylation (palmitate is shown in yellow) by an as yet uncharacterized PAT. Palmitoylated Rac1 segregates to cholesterol-rich, liquid-ordered domains (lipid rafts) in the plasma membrane and stabilizes these microdomains in a process associated with actin polymerization.
See this image and copyright information in PMC

References

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    1. del Pozo MA, Alderson NB, Kiosses WB, Chiang H-H, Anderson RGW, Schwartz MA (2004) Integrins regulate Rac targeting by internalization of membrane domains. Science (New York, NY) 303: 839–842 - PubMed
    1. Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R (1989) rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem 264: 16378–16382 - PubMed

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