Saitoh Shin-Ichiroh, Miyake Kensuke
Division of Infectious Genetics, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Chem Rec. 2006;6(6):311-9. doi: 10.1002/tcr.20093.
The Toll family of receptors senses microbial invasion and activates defense responses. Toll-like receptor 4 (TLR4) is a member of the Toll family that senses lipopolysaccharide (LPS), a principal membrane component from Gram-negative bacteria. LPS is known as an endotoxin that strongly activates immune cells such as macrophages and dendritic cells. LPS recognition by TLR4 requires an additional accessory molecule, MD-2. MD-2 is associated with the extracellular portion of TLR4, directly binds to LPS, and regulates subsequent LPS-induced TLR4 clustering. LPS recognition occurs on the cell surface. The subcellular distribution of TLR was shown to influence TLR responses. An endoplasmic reticulum (ER) chaperone, glycoprotein 96, is required for the stability of TLR4 and the formation of a TLR4/MD-2 complex in ER. MD-2 facilitates TLR4 glycosylation and its trafficking to the cell surface. Recently, another molecule, a protein associated with Toll-like receptor 4 (PRAT4A), was shown to play a critical role in cell surface expression of TLR4. These molecules control LPS responsiveness by regulating the subcellular distribution of TLR4.
Toll受体家族可感知微生物入侵并激活防御反应。Toll样受体4（TLR4）是Toll家族的成员之一，可感知脂多糖（LPS），LPS是革兰氏阴性菌的主要膜成分。LPS被称为内毒素，可强烈激活巨噬细胞和树突状细胞等免疫细胞。TLR4识别LPS需要另一种辅助分子MD-2。MD-2与TLR4的细胞外部分相关联，直接结合LPS，并调节随后LPS诱导的TLR4聚集。LPS识别发生在细胞表面。TLR的亚细胞分布显示会影响TLR反应。内质网（ER）伴侣糖蛋白96是TLR4稳定性以及在ER中形成TLR4/MD-2复合物所必需的。MD-2促进TLR4糖基化及其向细胞表面的转运。最近，另一种分子，即与Toll样受体4相关的蛋白（PRAT4A），被证明在TLR4的细胞表面表达中起关键作用。这些分子通过调节TLR4的亚细胞分布来控制LPS反应性。
