Daf-2

The daf-2 gene encodes an insulin-like receptor in the worm C. elegans. Mutations in daf-2 have been shown by Cynthia Kenyon to double the lifespan of the worms.^[1] The gene is known to regulate reproductive development, aging, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and also resistance to bacterial pathogens.^[2]

DAF-2 is the only insulin/IGF-1 like receptor in the worm. Insulin/IGF-1-like signaling is conserved from worms to humans. Unlike in higher eukaryotes, however, both human insulin as well as some insulin orthologs coded for by C. elegans' ins genes antagonize the DAF-2 receptor leading to inhibition of the pathway as opposed to activation of DAF-2 signaling.^[3] DAF-2 acts to negatively regulate the forkhead transcription factor Daf-16 through a phosphorylation cascade. Genetic analysis reveals that DAF-16 is required for daf-2-dependent lifespan extension and dauer formation. When not phosphorylated, DAF-16 is active and present in the nucleus.

References

1. ^ See publications documenting series of experiments at Cynthia Kenyon lab, in particular, Jennie B. Dorman, Bella Albinder, Terry Shroyer & Cynthia Kenyon, "The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans," Genetics, volume 141, number 4, pages 1399-1406 (1995); and Javier Apfeld & Cynthia Kenyon, "Cell non-autonomy of C. elegans daf-2 function in the regulation of diapause and lifespan," Cell, v. 95, n.2, pp.199-210 (1998).
2. ^ Minaxi S Gami and Catherine A Wolkow (2006). "Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for pharmacological manipulation of lifespan". Aging Cell 5 (1): 31–7. doi:10.1111/j.1474-9726.2006.00188.x. PMC 1413578. PMID 16441841. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1413578. 
3. ^ Pierce SB, Costa M, Wisotzkey R, Devadhar S, Homburger SA, Buchman AR, Ferguson KC, Heller J, Platt DM, Pasquinelli AA, Liu LX, Doberstein SK, Ruvkun G. (march 2001). "Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family". Genes dev 15 (6): 672–86. doi:10.1101/gad.867301. PMC 312654. PMID 11274053. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=312654. 

External links

• WormBase entry for daf-2