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