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A general role for TANGO1, encoded by MIA3, in secretory pathway organization and function.
Journal of Cell Science ( IF 3.3 ) Pub Date : 2021-09-07 , DOI: 10.1242/jcs.259075
Janine McCaughey 1 , Nicola L Stevenson 1 , Judith M Mantell 2 , Chris R Neal 2 , Alex Paterson 3 , Kate Heesom 4 , David J Stephens 1
Affiliation  

Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum (ER), which is an essential process in eukaryotic cells. In vertebrates, the MIA3 gene encodes two major forms of transport and Golgi organization protein 1 (TANGO1S and TANGO1L), which have previously been implicated in selective trafficking of procollagen. Using genome engineering of human cells, light microscopy, secretion assays, genomics and proteomics, we show that disruption of the longer form, TANGO1L, results in relatively minor defects in secretory pathway organization and function, including having limited impacts on procollagen secretion. In contrast, loss of both long and short forms results in major defects in cell organization and secretion. These include a failure to maintain the localization of ERGIC53 (also known as LMAN1) and SURF4 to the ER-Golgi intermediate compartment and dramatic changes to the ultrastructure of the ER-Golgi interface. Disruption of TANGO1 causes significant changes in early secretory pathway gene and protein expression, and impairs secretion not only of large proteins, but of all types of secretory cargo, including small soluble proteins. Our data support a general role for MIA3/TANGO1 in maintaining secretory pathway structure and function in vertebrate cells.

中文翻译:


由 MIA3 编码的 TANGO1 在分泌途径组织和功能中的一般作用。



需要复杂的机械来驱动内质网(ER)的分泌物输出,这是真核细胞的一个重要过程。在脊椎动物中,MIA3 基因编码两种主要形式的运输和高尔基体组织蛋白 1(TANGO1S 和 TANGO1L),这些蛋白先前被认为与前胶原的选择性运输有关。利用人类细胞的基因组工程、光学显微镜、分泌测定、基因组学和蛋白质组学,我们发现较长形式 TANGO1L 的破坏会导致分泌途径组织和功能相对较小的缺陷,包括对前胶原分泌的影响有限。相反,长形式和短形式的丢失会导致细胞组织和分泌的重大缺陷。这些包括无法维持ERGIC53(也称为LMAN1)和SURF4在ER-高尔基体中间室的定位,以及ER-高尔基体界面超微结构的巨大变化。 TANGO1 的破坏会导致早期分泌途径基因和蛋白质表达的显着变化,并且不仅损害大蛋白质的分泌,而且损害所有类型的分泌货物,包括小可溶性蛋白质。我们的数据支持 MIA3/TANGO1 在维持脊椎动物细胞分泌途径结构和功能中的一般作用。
更新日期:2021-09-07
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