TANGO1 and Mia2/cTAGE5 (TALI) cooperate to export bulky pre-chylomicrons/VLDLs from the endoplasmic reticulum.
TANGO1 and Mia2/cTAGE5 (TALI) cooperate to export bulky pre-chylomicrons/VLDLs from the endoplasmic reticulum.
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DOI：
10.1083/jcb.201603072
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发表时间：
2016-05-09
期刊：
影响因子：
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通讯作者：
Malhotra V
中科院分区：
文献类型：
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作者：
Santos AJ;Nogueira C;Ortega-Bellido M;Malhotra V
Santos等人。研究表明，TANGO1和一种类似TANGO1的蛋白TALI相互结合，共同发挥受体的作用，将含有载脂蛋白B的巨大脂肪颗粒从内质网中排出。然而，TANGO1介导的粗大胶原蛋白由相同的细胞输出是不依赖TALI的。前胶原蛋白、前乳糜粒和前极低密度脂蛋白(前极低密度脂蛋白)太大，无法装入传统的COPII包裹的小泡中，那么这些笨重的货物是如何从内质网(ER)输出的？我们已经证明，位于内质网出口部位的TANGO1是前胶原输出所必需的。我们报道了TANGO1和TANGO1样蛋白(TALI)，一种由MiA2和cTAGE5基因产物融合产生的嵌合蛋白，在内质网输出前乳糜粒和前VLDL中所起的作用。TANGO1与TALI结合，两者都与载脂蛋白B(ApoB)相互作用，对于含ApoB的脂质颗粒募集到ER出口部位并随后出口是必需的。虽然ApoB的输出需要TANGO1和TALI两种功能，但同一细胞输出XII前胶原只需要TANGO1。这些发现揭示了TANGO1在ER出口笨重货物中的一般作用，并确定了TALI在协助TANGO1出口笨重脂肪颗粒方面的特定要求。
Santos et al. show that TANGO1 and a TANGO1-like protein, TALI, bind each other and function together as receptors to export bulky ApoB-containing lipid particles from the endoplasmic reticulum. However, TANGO1-mediated export of bulky collagens by the same cells is TALI independent. Procollagens, pre-chylomicrons, and pre–very low-density lipoproteins (pre-VLDLs) are too big to fit into conventional COPII-coated vesicles, so how are these bulky cargoes exported from the endoplasmic reticulum (ER)? We have shown that TANGO1 located at the ER exit site is necessary for procollagen export. We report a role for TANGO1 and TANGO1-like (TALI), a chimeric protein resulting from fusion of MIA2 and cTAGE5 gene products, in the export of pre-chylomicrons and pre-VLDLs from the ER. TANGO1 binds TALI, and both interact with apolipoprotein B (ApoB) and are necessary for the recruitment of ApoB-containing lipid particles to ER exit sites for their subsequent export. Although export of ApoB requires the function of both TANGO1 and TALI, the export of procollagen XII by the same cells requires only TANGO1. These findings reveal a general role for TANGO1 in the export of bulky cargoes from the ER and identify a specific requirement for TALI in assisting TANGO1 to export bulky lipid particles.