Lipid raft localization of TLR2 and its co-receptors is independent of membrane lipid composition
Lipid raft localization of TLR2 and its co-receptors is independent of membrane lipid composition
复制标题
DOI：
10.7717/peerj.4212
复制
发表时间：
2018-01-05
期刊：
影响因子：
2.7
通讯作者：
Schumann, Julia
中科院分区：
文献类型：
--
作者：
Hellwing, Christine;Schoeniger, Axel;Schumann, Julia
背景。 Toll 样受体 (TLR) 是一类重要且进化保守的模式识别受体，与先天免疫相关。革兰氏阳性细胞壁成分的识别强烈依赖于 TLR2。为了发挥功能，TLR2 主要与 TLR1 或 TLR6 在专门的膜微域（脂筏）内形成异二聚体。膜脂组成和脂筏的理化性质会受到外源脂肪酸的修饰。我们小组之前的研究提供了证据，表明用多不饱和脂肪酸（PUFA）富集巨噬细胞会基于补充的PUFA及其延伸和去饱和产物的掺入诱导脂筏和非脂筏的重新排序。方法。在本研究中，我们研究了膜微域重组对脂筏内 TLR2 及其共受体 TLR1 和 TLR6 聚类的潜在限制作用。为此，RAW264.7 巨噬细胞补充了二十二碳六烯酸 (DHA) 或花生四烯酸 (AA)，并分析了 TLR 刺激背景下的受体表达和微域定位。结果和结论。我们的分析表明，补充 PUFA 后受体水平和微区定位没有变化。与 TLR4 信号级联反应相反，TLR2 通路在膜水平上不受外源 PUFA 的影响。
Background. Toll like receptors (TLRs) are an important and evolutionary conserved class of pattern recognition receptors associated with innate immunity. The recognition of Gram-positive cell wall constituents strongly depends on TLR2. In order to be functional, TLR2 predominantly forms a heterodimer with TLR1 or TLR6 within specialized membrane microdomains, the lipid rafts. The membrane lipid composition and the physicochemical properties of lipid rafts are subject to modification by exogenous fatty acids. Previous investigations of our group provide evidence that macrophage enrichment with polyunsaturated fatty acids (PUFA) induces a reordering of lipid rafts and non-rafts based on the incorporation of supplemented PUFA as well as their elongation and desaturation products.Methods. In the present study we investigated potential constraining effects of membrane microdomain reorganization on the clustering of TLR2 with its co-receptors TLR1 and TLR6 within lipid rafts. To this end, RAW264.7 macrophages were supplemented with either docosahexaenoic acid (DHA) or arachidonic acid (AA) and analyzed for receptor expression and microdomain localization in context of TLR stimulation.Results and Conclusions. Our analyses showed that receptor levels and microdomain localization were unchanged by PUFA supplementation. The TLR2 pathway, in contrast to the TLR4 signaling cascade, is not affected by exogenous PUFA at the membrane level.