Toll (gene)
The Toll genes encode members of the Toll-like receptor class of proteins. "Toll" is German for "amazing" or "great".[1] Mutants in the Toll gene were originally identified by 1995 Nobel Laureates Christiane Nüsslein-Volhard and Eric Wieschaus and colleagues in the fruit fly Drosophila melanogaster in 1985[2], and cloned by the laboratory of Kathryn Anderson in 1988.[3] Since then, eleven mammalian Toll genes have been identified.
In flies, Toll was first identified as a gene important in embryogenesis in establishing the dorsal-ventral axis. In 1996, Toll was found to have a role in the fly's immunity to fungal infections[4]. Both mammalian and invertebrate Toll genes are required for innate immunity.
Toll-like receptors in mammals were identified in 1997 at Yale University by Ruslan Medzhitov and Charles Janeway.[5] Concurrently, Bruce A. Beutler and colleagues discovered that the Toll-like receptors (TLRs) act as the principal sensors of infection in mammals. This latter discovery hinged on the positional cloning of the mammalian lipopolysaccharide (LPS) response locus, which identified the LPS receptor as Toll related protein TLR4.[6]
The name of the gene family derives from Christiane Nüsslein-Volhard's 1985 exclamation, "Das ist ja toll!"[2] The exclamation, which translates as "That's amazing!" or "That's weird!", was in reference to the underdeveloped ventral portion of a fruit fly larva.
[edit] References
- ^ "toll - LEO Deutsch-English Worterbuch". http://dict.leo.org/ende?lp=ende&p=CqhggsWkAA&search=toll&trestr=0x8004. Retrieved 2011-10-03.
- ^ a b Hansson GK, Edfeldt K (2005). "Toll to be paid at the gateway to the vessel wall". Arterioscler. Thromb. Vasc. Biol. 25 (6): 1085–7. doi:10.1161/01.ATV.0000168894.43759.47. PMID 15923538. http://atvb.ahajournals.org/cgi/content/full/25/6/1085.
- ^ Hashimoto C, Hudson KL, Anderson KV (1988). "The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein". Cell 52 (2): 269–79. doi:10.1016/0092-8674(88)90516-8. PMID 2449285.
- ^ Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996). "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults". Cell 86 (6): 973–983. doi:10.1016/S0092-8674(00)80172-5. PMID 8808632.
- ^ Medzhitov R, Preston-Hurlburt P, Janeway CA (1997). "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity". Nature 388 (6640): 394–7. doi:10.1038/41131. PMID 9237759.
- ^ Poltorak, Alexander; et al. (1998). "Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene". Science 282 (5396): 2085–2088. doi:10.1126/science.282.5396.2085. PMID 9851930.
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