Distinct roles of TIR and non-TIR regions in the subcellular localization and signaling properties of MyD88

Edited by Masayuki Miyasaka

Received 19 May 2007; accepted 6 June 2007. published online 19 June 2007.

Abstract

MyD88 is a cytoplasmic adaptor protein that is critical for Toll-like receptor (TLR) signaling. The subcellular localization of MyD88 is characterized as large condensed forms in the cytoplasm. The mechanism and significance of this localization with respect to the signaling function, however, are currently unknown. Here, we demonstrate that MyD88 localization depends on the entire non-TIR region and that the correct cellular targeting of MyD88 is indispensable for its signaling function. The Toll-interleukin I receptor-resistance (TIR) domain does not determine the subcellular localization, but it mediates interaction with specific TLRs. These findings reveal distinct roles for the TIR and non-TIR regions in the subcellular localization and signaling properties of MyD88.

Abbreviations: CFP, cyan fluorescent protein, CTXb, cholera toxin subunit b, DD, death domain, TIR, Toll-interleukin I receptor-resistance, TLR, Toll-like receptor, YFP, yellow fluorescent protein, INT, Intermediate region

Keywords: MyD88, Non-TIR region, Signal transduction, Subcellular localization, TIR domain, TLR

Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan

Corresponding author. Fax: +81 11 706 7824.

PII: S0014-5793(07)00656-4

doi:10.1016/j.febslet.2007.06.008

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