Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene: Myd88 - Myd88

Drosophila melanogaster

Synonyms: CG2078, DMMYD88, dMyD88, EP(2)2535, kra, Kra, krapfen, LD20892, MyD88

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Hardiman, G., Hardiman, G., Horng, T., Yamagata, M., Schnare, M., et al.

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Disease relevance of Myd88

Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections [1].

High impact information on Myd88

Intracellular signalling mechanisms mediated by TIRs are similar, with MyD88 (refs 5-8) and TRAF6 (refs 9, 10) having critical roles [2].
Finally, our findings implicate MyD88 as a general adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity [3].
The complex of MyD88 and Tube forms prior to signaling and is localized to the embryonic plasma membrane by MyD88 [4].
We also show that dMyD88 associates with the death domain-containing adapter Drosophila Fas-associated death domain-containing protein (dFADD), which in turn interacts with the apical caspase Dredd [5].
Here, we report that recognition of CpG DNA requires MyD88, an adaptor protein involved in signal transduction by the Toll-like receptors (TLRs), essential components of innate immune recognition in both Drosophila and mammals [1,2] [6].

Biological context of Myd88

Experiments in cultured cells reveal that the fly orthologue of the adaptor protein MyD88 is essential for signal transduction from Toll to a second adaptor protein, Tube [7].
MyD88 was localized to the distal region of mouse chromosome 9 by interspecific backcross mapping [8].
Here, I demonstrate that the open reading frame of MyD88, a gene induced in myeloid differentiation, is related to the cytoplasmic domains of the interleukin-1 receptor and the Toll gene product [9].

Anatomical context of Myd88

The expression pattern of MyD88 is also more widespread than originally believed: a 2.6 kb hMyD88 mRNA species was found to be constitutively expressed in many adult human tissues; in addition MyD88 expression was observed in monocyte, T, B, NK and dendritic cells [10].
Interestingly, many aa residues conserved among the insect Toll-like cytoplasmic domains are also conserved in mammalian and avian type-I interleukin-1 receptors and the hypothetical product of a transcript, MyD88, found in murine myeloid cells [11].
Northern blot analysis revealed widespread expression of MyD88 in many adult mouse tissues, and RT-PCR studies detected MyD88 mRNA in T and B cell lines and differentiating embryonic stem cells [8].
Although various microbial cell-wall components are recognized by different receptors, all of these responses are abrogated in MyD88-deficient cells [12].

Other interactions of Myd88

Drosophila MyD88 is an adapter in the Toll signaling pathway [5].
These genes, which include Sos and Myd88, represent putative targets for miRNA regulation [13].

References

Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Tauszig-Delamasure, S., Bilak, H., Capovilla, M., Hoffmann, J.A., Imler, J.L. Nat. Immunol. (2002)
Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Suzuki, N., Suzuki, S., Duncan, G.S., Millar, D.G., Wada, T., Mirtsos, C., Takada, H., Wakeham, A., Itie, A., Li, S., Penninger, J.M., Wesche, H., Ohashi, P.S., Mak, T.W., Yeh, W.C. Nature (2002)
MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C., Ghosh, S., Janeway, C.A. Mol. Cell (1998)
Regulated assembly of the Toll signaling complex drives Drosophila dorsoventral patterning. Sun, H., Towb, P., Chiem, D.N., Foster, B.A., Wasserman, S.A. EMBO J. (2004)
Drosophila MyD88 is an adapter in the Toll signaling pathway. Horng, T., Medzhitov, R. Proc. Natl. Acad. Sci. U.S.A. (2001)
Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Schnare, M., Holt, A.C., Takeda, K., Akira, S., Medzhitov, R. Curr. Biol. (2000)
A heterotrimeric death domain complex in Toll signaling. Sun, H., Bristow, B.N., Qu, G., Wasserman, S.A. Proc. Natl. Acad. Sci. U.S.A. (2002)
Genetic structure and chromosomal mapping of MyD88. Hardiman, G., Jenkins, N.A., Copeland, N.G., Gilbert, D.J., Garcia, D.K., Naylor, S.L., Kastelein, R.A., Bazan, J.F. Genomics (1997)
Macrophage differentiation marker MyD88 is a member of the Toll/IL-1 receptor family. Hultmark, D. Biochem. Biophys. Res. Commun. (1994)
Molecular characterization and modular analysis of human MyD88. Hardiman, G., Rock, F.L., Balasubramanian, S., Kastelein, R.A., Bazan, J.F. Oncogene (1996)
Interspecific comparisons reveal conserved features of the Drosophila Toll protein. Yamagata, M., Merlie, J.P., Sanes, J.R. Gene (1994)
Toll-like receptors: lessons from knockout mice. Akira, S. Biochem. Soc. Trans. (2000)
Developmental defects by antisense-mediated inactivation of micro-RNAs 2 and 13 in Drosophila and the identification of putative target genes. Boutla, A., Delidakis, C., Tabler, M. Nucleic Acids Res. (2003)