Disease relevance of 18w

• In the absence of the 18W receptor, larvae are more susceptible to bacterial infection [1].
• 18-Wheeler does not qualify as a pattern recognition receptor of Gram-negative bacteria [2].
• Here we demonstrate that the Drosophila metalloprotease tolloid-related (tlr) is required for proper fasciculation/defasciculation of motor axons in the CNS and for normal guidance of many motor axons enroute to their muscle targets [3].
• We have previously reported that Toll-like receptor (TLR) 2 mRNA was induced after infection with Mycobacterium avium [4].
• Paralogous members of the Toll-like receptor (TLR) family sense infection and ignite the systemic inflammatory reaction that is known as sepsis [5].

High impact information on 18w

• Recent genetic evidence has shown that a mammalian Toll-like receptor, mouse Tlr4, is the signal transducing receptor activated by bacterial lipopolysaccharide [6].
• 18-wheeler is expressed in the larval fat body, the primary organ of antimicrobial peptide synthesis [1].
• Toll-6, -7, and -8, on the other hand, are expressed at high levels during embryogenesis and molting, suggesting that, like Toll and 18w, they perform developmental functions [7].
• Two of these, Toll-like receptor (TLR)2 and TLR4, recently were shown to play a critical role in innate immunity against bacteria [7].
• Induction of neuron-specific glycosylation by Tollo/Toll-8, a Drosophila Toll-like receptor expressed in non-neural cells [8].

Biological context of 18w

• Analysis of the expression of 18w in different mutant backgrounds shows that it is under control of segment polarity and homeotic genes [9].
• The data suggest that the 18W protein participates in the developmental program specified by segmentation and homeotic genes as a cell adhesion or receptor molecule that facilitates cell movements [9].
• The Drosophila 18 wheeler is required for morphogenesis and has striking similarities to Toll [9].
• Genetic and molecular mapping of the relevant locus reveals that Tollo/Toll-8, a member of the Toll-like receptor family, is altered on the TM3 chromosome [8].
• Quantitative complementation tests performed for 45 positional candidate genes within these intervals revealed 7 genes that failed to complement the QTL: eagle, 18 wheeler, Enhancer of split, Polycomb, spermatocyte arrest, l(2)05510, and l(2)k02206 [10].

Anatomical context of 18w

• Toll-like receptor mRNA expression patterns in human dendritic cells and monocytes [11].
• Expression of 18-wheeler in the follicle cell epithelium affects cell migration and egg morphology in Drosophila [12].

Associations of 18w with chemical compounds

• The activity of a Toll-like receptor, called Tollo/Toll-8, induces a pattern of incompletely defined, but neural specific, glycan expression in the Drosophila embryo [13].
• Sequence analysis indicates that 18w encodes a transmembrane protein with an extracellular moiety containing many leucine rich repeats and cysteine motifs, and an intracellular domain bearing homology to the cytoplasmic portion of the interleukin-1-receptor [9].

Other interactions of 18w

• The 18w mutation particularly affects the induction of AttC, which may be a useful marker for 18w signaling [14].
• Although markers in SR-CII and 18-wheeler explain >20% of the phenotypic variation in resistance to L. lactis and E. faecalis, respectively, most of the molecular polymorphisms tested explain <10% of the total variance in bacterial load sustained after infection [15].
• Segmental modulation of tlr expression later in the tracheal system is dependent upon the function of the homeotic genes of the bithorax complex [16].

References