Toll (gene)

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The Toll genes encode members of the Toll-like receptor class of proteins. ("Toll" is German for "amazing" or "mad".)[1] Toll genes were originally identified in the fruit fly Drosophila melanogaster in 1985, [2] , and cloned in 1988.[3] Since then, eleven known 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. 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.[4]. 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 TLR4 [5].

Their name derives from Christiane Nüsslein-Volhard's 1985 exclamation, "Das war ja toll!"[2] The exclamation, which translates as "That's weird!", was in reference to the underdeveloped posterior portion of a fruit fly larva.


[edit] References

  1. ^ toll - Wiktionary, das freie Wörterbuch – Das Wikiwörterbuch. Retrieved on 2007-11-10.
  2. ^ 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. 
  3. ^ 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. PMID 2449285. 
  4. ^ 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. 
  5. ^ Alexander Poltorak, Xiaolong He, * Irina Smirnova, Mu-Ya Liu, dagger Christophe Van Huffel, ddagger Xin Du, Dale Birdwell, Erica Alejos, Maria Silva, Chris Galanos, Marina Freudenberg, Paola Ricciardi-Castagnoli, Betsy Layton, Bruce Beutler § Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene http://www.sciencemag.org/cgi/content/abstract/282/5396/2085

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