Toll (gene family)

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The toll genes encode members of the toll-like receptor class of proteins. 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,[1] and cloned by the laboratory of Kathryn Anderson in 1988.[2] Since then, thirteen 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.[3] 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, two separate studies, led by Shizuo Akira, Bruce A. Beutler and their respective colleagues discovered that the Toll-like receptors (TLRs) act as the principal sensors of infection in mammals.[5][6]

The name of the gene family derives from Christiane Nüsslein-Volhard's 1985 exclamation, "Das ist ja toll!"[1] The exclamation, which translates as "That's amazing!" was in reference to the underdeveloped ventral portion of a fruit fly larva. The adjective "toll" is German for "amazing" or "great".[7]

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  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  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. ^ Hoshino, K; Takeuchi, O; Kawai, T; Sanjo, H; Ogawa, T; Takeda, Y; Takeda, K; Akira, S (Apr 1, 1999). "Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product". Journal of Immunology. 162 (7): 3749–52. PMID 10201887.
  6. ^ 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.
  7. ^ "toll - LEO Deutsch-English Worterbuch". Retrieved 2011-10-03.

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