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Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.


ABSTRACT: Collagen is the most abundant protein in animals. Its dysregulation contributes to aging and many human disorders, including pathological tissue fibrosis in major organs. How premature collagen proteins in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNA interference screen, we identified an uncharacterized Caenorhabditis elegans gene tmem-131, deficiency of which impairs collagen production and activates ER stress response. We find that amino termini of human TMEM131 contain bacterial PapD chaperone-like domains, which recruit premature collagen monomers for proper assembly and secretion. Carboxy termini of TMEM131 interact with TRAPPC8, a component of the TRAPP tethering complex, to drive collagen cargo trafficking from ER to the Golgi. We provide evidence that previously undescribed roles of TMEM131 in collagen recruitment and secretion are evolutionarily conserved in C. elegans, Drosophila, and humans.

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC7015688 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.

Zhang Zhe Z   Bai Meirong M   Barbosa Guilherme Oliveira GO   Chen Andrew A   Wei Yuehua Y   Luo Shuo S   Wang Xin X   Wang Bingying B   Tsukui Tatsuya T   Li Hao H   Sheppard Dean D   Kornberg Thomas B TB   Ma Dengke K DK  

Science advances 20200212 7


Collagen is the most abundant protein in animals. Its dysregulation contributes to aging and many human disorders, including pathological tissue fibrosis in major organs. How premature collagen proteins in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNA interference screen, we identified an uncharacterized <i>Caenorhabditis elegans</i> gene <i>tmem-131</i>, deficiency of which impairs collagen production and activates ER stress response.  ...[more]

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