The role of MyD88-like adapters in Toll-like receptor signal transduction.

Signal-transduction pathways activated by Toll-like receptors (TLRs) have been the subject of intense investigation because of the key role played by TLRs in the recognition and elimination of microbes. Signalling is initiated by a domain termed the Toll/interleukin-1 (IL-1) receptor (TIR) domain that occurs on the cytosolic face of TLRs. This recruits, via homotypic interactions, adapter proteins that contain TIR domains. Three such adapter proteins have been discovered to date, and have been named MyD88, Mal [MyD88 adapter-like; also known as TIRAP (TIR domain-containing adapter protein)] and Trif (TIR-domain-containing adapter inducing interferon-beta). Differences are emerging between TLRs in terms of which adapter is recruited by which TLR. This may lead to specificities in TLR signalling, with pathways being triggered that are specific for the elimination of the invading microbe. However, signals that separate Mal from MyD88 have yet to emerge, although biochemical differences between the two proteins imply that each will have a specific function.