Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting
Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting
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DOI：
10.1074/jbc.m602794200
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发表时间：
2006-10-13
影响因子：
4.8
通讯作者：
Triantafilou, Kathy
中科院分区：
文献类型：
--
作者：
Triantafilou, Martha;Gamper, Frederick G. J.;Triantafilou, Kathy
Toll样受体(TLRs)是天然免疫系统的受体，负责识别病原体相关的分子模式。TLR2似乎是最混杂的TLR受体，能够识别最多样化的病原体相关模式。它的混杂被归因于它与TLR 1和6异源二聚的独特能力，以及最近它与CD36的结合，以响应二酰化的脂蛋白。因此，TLR2似乎形成了对不同微生物配体的反应的受体簇。在这项研究中，我们研究了TLR2细胞表面对不同配体的异型相互作用以及内化和细胞内转运。我们的数据表明，TLR2与TLR1和TLR6形成异二聚体，并且这些异二聚体是预先存在的，不是由配体诱导的。在特定配体的刺激下，这些异源二聚体被招募到脂筏中。相反，TLR2/6与CD36的异型关联不是预先形成的，而是由配体诱导的。所有的TLR2受体簇都聚集在脂筏中，并以高尔基体为靶标。这种定位和靶向是特定于配体的。激活发生在细胞表面，观察到的运输与信号无关。
Toll-like receptors (TLRs) are receptors of the innate immune system responsible for recognizing pathogen-associated molecular patterns. TLR2 seems to be the most promiscuous TLR receptor able to recognize the most diverse set of pathogen-associated patterns. Its promiscuity has been attributed to its unique ability to heterodimerize with TLRs 1 and 6 and, most recently, to its association with CD36 in response to diacylated lipoproteins. Thus, it seems that TLR2 forms receptor clusters in response to different microbial ligands. In this study we investigated TLR2 cell surface heterotypic interactions in response to different ligands as well as internalization and intracellular trafficking. Our data show that TLR2 forms heterodimers with TLR1 and TLR6 and that these heterodimer pre-exist and are not induced by the ligand. Upon stimulation by the specific ligand, these heterodimers are recruited within lipid rafts. In contrast, heterotypic associations of TLR2/6 with CD36 are not preformed and are ligand-induced. All TLR2 receptor clusters accumulate in lipid rafts and are targeted to the Golgi apparatus. This localization and targeting is ligand-specific. Activation occurs at the cell surface, and the observed trafficking is independent of signaling.