Toll-like Receptor Influences Glycosylation

Science's STKE  25 Feb 2003:
Vol. 2003, Issue 171, pp. tw77-TW77
DOI: 10.1126/stke.2003.171.tw77

The surface of eukaryotic cells is decorated with carbohydrates that serve as discriminating markers in numerous cell, tissue, and stage-specific processes including cell recognition, adhesion and migration, and cell signaling. Seppo et al. report that mutation of a gene that encodes a Toll-like receptor (TLR) Tollo (the Drosophila homolog of mammalian Toll-8) alters glycosylation in Drosophila. TLRs function in development in Drosophila and in the innate immune response of Drosophila and vertebrates by transducing pattern recognition signals that are frequently glycan-based (see the review by Dunne and O'Neill). Recognition of an N-linked oligosaccharide epitope in neural tissue by a specific antibody was abolished in flies harboring a disrupted tollo gene. However, the epitope was still recognized in nonneural tissue. Tollo is expressed in embryonic ectoderm during periods of maximal contact with neural precursor cells, but then disappears once neurons segregate from the ectoderm. Flies lacking Tollo exhibited axon defasciculation errors. Neural-specific glycosylation could be rescued by expression of transgenic tollo in nonneural cells. The study suggests that Tollo-expressing cells modulate glycan expression in adjacent cells, possibly through binding to a neuronal surface protein. This interaction may produce appropriate spatial and temporal patterns of cell-specific glycosylation during development and offers a broad mechanism by which TLRs could operate in cell surveillance and recognition.

A. Seppo, P. Matani, M. Sharrow, M. Tiemeyer, Induction of neuron-specific glycosylation by Tollo/Toll-8, a Drosophila Toll-like receptor expressed in non-neural cells. Development 130, 1439-1448 (2003) [Abstract] [Full Text]

A. Dunne, L. A. J. O'Neill, The interleukin-1 receptor/Toll-like receptor superfamily: Signal transduction during inflammation and host defense. Sci. STKE 2003, re3 (2003). [Full Text]