CDH1 后翻译加工及转运至细胞膜
中文名称
通路描述
CDH1（也称为 E-cadherin、上皮钙粘蛋白、Cadherin-1 或 uvomorulin）以约 140 kDa 的前体蛋白形式合成。N 端信号肽（氨基酸残基 1-22）在内质网（ER）中被移除，而 CDH1 的前蛋白区域（氨基酸残基 23-154）在转-Golgi 网络中被切割，形成约 120 kDa 的蛋白。虽然 CDH1 在细胞膜上的展示不需要蛋白酶解，但它是建立粘附连接处同源相互作用所必需的。CDH1 的前蛋白序列主要由 FURIN 去除，但也涉及其他前蛋白转化酶。与其他细胞膜蛋白类似，CDH1 在多个氨基酸残基上发生糖基化。CDH1 中的四个糖基化天冬酰胺残基与 ER 中通过 OST 复合物转移的预组装高甘露糖寡糖 Glu3Man9GlucNAc2 糖基化序列相符（Ramírez et al. 2019）。CDH1 上四个天冬酰胺残基的 N-糖基化，特别是 N637，对于 CDH1 的正确折叠和转运至 Golgi 进行进一步加工是必需的（Zhou et al. 2008; Zhao H. et al. 2008）。在果蝇中，编码一种参与 Glu3Man9GlucNAc2 寡糖前体末端葡萄糖残基添加的酶 Xiantuan（也称为 xit，酵母 ALG8 的同源物）对于 E-cadherin 的正确糖基化和细胞内分布是必需的（Zhang et al. 2014）。CDH1 在内质网中也发生 O-甘露糖化，TMTC3 是其中涉及的 ER 甘露糖转移酶之一（Graham et al. 2020）。CDH1 在内质网中后翻译加工期间与β-猫enin（CTNNB1）结合（Chen et al. 1999）。在 Golgi 中，CDH1 可能由 GALNT3 催化进一步糖基化，将 O-GalNAc 基团转移到目标蛋白上（Wang et al. 2014; Raghu et al. 2019; Shu et al. 2023）。在凋亡期间，ER 压力导致 CTNNB1 和 CDH1 胞质尾部的 O-糖基化，阻止 CDH1 从 ER 退出，并减少细胞间粘附（Zhu et al. 2001; Geng et al. 2012）。CDH1 从 Golgi 转运至细胞膜受到 RAB2A 的负向调节（Kajiho et al. 2016）。Golgi 膜蛋白 TMEM165 也被报道通过影响 CDH1 糖基化来负向调节 CDH1 转运至细胞膜（Murali et al. 2020）。CDH1 糖基化在癌症中被发现发生改变（Yoshimura et al. 1996; Byrne et al. 2012; 综述在 Zhao Y. et al. 2008; 综述在 Bastian et al. 2021），这会影响 CTNNB1 信号传导（Kitada et al. 2001）。据报道，CDH1 的细胞类型特异性加工也存在（Burke and Hong 2006）。CDH1 转运至细胞表面的过程可受细胞汇合度依赖性调节，因此亚汇合细胞呈现较少的 CDH1（Murray et al. 2004）。CDH1 的糖基化也被报道在汇合细胞和亚汇合细胞之间有所不同（Liwosz et al. 2006）。
英文描述
Assembly and release of respiratory syncytial virus (RSV) virions A mature virion of the respiratory syncytial virus (RSV) consists of the ribonucleoprotein complex (RNP) surrounded by the protein matrix and a lipid bilayer envelope. The RNP is composed of the genomic negative sense single-stranded (-ssRNA) that is tightly associated with the N protein (nucleoprotein) and the RNA-dependent RNA polymerase complex (RdRP). The RdRP consists of the L protein subunit (large polymerase subunit), the P protein subunit (phosphoprotein polymerase cofactor), and the M2-1 protein, which acts as a transcription processivity factor. The matrix consists of the M (matrix) protein. The M2-1 protein serves as the bridge between the RNP and the M protein. The matrix supports the viral envelope. The viral envelope contains three embedded viral proteins: fusion protein (F), attachment protein (G), and a small hydrophobic protein (SH). The M protein associates with the cytoplasmic domain of the F protein. The SH protein forms a pentameric ion channel in the viral envelope and is thought to delay apoptosis of infected cells. The assembly and budding of RSV virions primarily occurs at the apical surface of ciliated airway epithelial cells where viral filaments containing RNPs form. The budding of RSV virions requires interactions between viral proteins, host cytoskeletal proteins, and membrane. For review, please refer to Shaikh and Crowe 2013, and Battles and McLellan 2019.
Based on the findings that P, M, and F proteins are sufficient for formation of viralâlike particles (VLPs), P protein, particularly its highly phosphorylated serine/threonineârich region between amino acids 39 and 57 that likely interacts with M and/or F proteins, may play an important role in the assembly (Meshram and Oomens 2019).
Based on the findings that P, M, and F proteins are sufficient for formation of viralâlike particles (VLPs), P protein, particularly its highly phosphorylated serine/threonineârich region between amino acids 39 and 57 that likely interacts with M and/or F proteins, may play an important role in the assembly (Meshram and Oomens 2019).
所含基因
6 个基因