内体 TLR 的运输与加工
中文名称
通路描述
哺乳动物 TLR3、TLR7、TLR8 和 TLR9 是内体受体，它们感知从内吞/吞噬细菌、病毒或寄生虫中释放的核酸。这些 TLR 具有面向内体腔的配体识别基序（该腔室在拓扑上等同于细胞外）、跨膜基序和面向胞质的信号基序。在正常条件下，由于受体 compartmentalization、运输和蛋白酶体加工等多层调节，TLRs 不识别自核酸。在稳态下，TLR3、TLR7、TLR8 和 TLR9 主要存在于内质网 (ER)，但它们在特定配体激活下仅在酸化的内溶酶体 compartment 中激活 (Hacker H et al 1998, Funami K et al 2004, Gibbard RJ et al 2006)。一些伴侣蛋白与 TLRs 在 ER 中结合，以促进其向内溶酶体的高效转运。当到达内溶酶体 compartment 时，TLR7 和 TLR9 的胞外基序被半胱氨酸内肽酶蛋白消化。TLR9 全长和 C 端切割后均结合 CpG 寡核苷酸，但有人认为只有切割后的受体才是功能性的。尽管 Ewald 等人 2011 年报道了 TLR3 的类似切割，但其他研究表明 TLR3 胞外基序的 N 端区域涉及配体结合，因此 TLR3 可能作为全长受体发挥作用 (Liu L et al 2008, Tokisue T et al 2008)。关于 TLR8 的切割尚无数据，尽管 TLR8 的细胞生物学可能类似于 TLR9 和 TLR7 (Gibbard RJ et al 2006, Wei T et al 2009)。
英文描述
Trafficking and processing of endosomal TLR Mammalian TLR3, TLR7, TLR8, TLR9 are endosomal receptors that sense nucleic acids that have been released from endocytosed/phagocytosed bacteria, viruses or parasites. These TLRs have a ligand-recognition domain that faces the lumen of the endosome (which is topologically equivalent to the outside of the cell), a transmembrane domain, and a signaling domain that faces the cytosol.Under normal conditions, self nucleic acids are not recognized by TLRs due to multiple levels of regulation including receptor compartmentalization, trafficking and proteolytic processing (Barton GM et al 2006, Ewald SE et al 2008). At steady state TLR3, TLR7, TLR8, TLR9 reside primarily in the endoplasmic reticulum (ER), however, their activation by specific ligands only occurs within acidified endolysosomal compartments (Hacker H et al 1998, Funami K et al 2004, Gibbard RJ et al 2006). Several chaperon proteins associate with TLRs in the ER to provide efficient translocation to endolysosome. Upon reaching endolysosomal compartments the ectodomains of TLR7 and TLR9 are proteolytically cleaved by cysteine endoproteases. Both full-length and cleaved C-terminus of TLR9 bind CpG-oligodeoxynucleotides, however it has been proposed that only the processed receptor is functional. Although similar cleavage of TLR3 has been reported by Ewald et al 2011, other studies demonstrated that the N-terminal region of TLR3 ectodomain was implicated in ligand binding, thus TLR3 may function as a full-length receptor (Liu L et al 2008, Tokisue T et al 2008). There are no data on TLR8 processing, although the cell biology of TLR8 is probably similar to TLR9 and TLR7 (Gibbard RJ et al 2006, Wei T et al 2009).
所含基因
13 个基因