Hits:

Title of Paper:The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response

Journal:PLoS Genetics

Summary:Dysregulation of collagen production and secretion contributes to aging and tissue fibrosis of major organs. How procollagen proteins in the endoplasmic reticulum (ER) route as specialized cargos for secretion remains to be fully elucidated. Here, we report that TMEM39, an ER-localized transmembrane protein, regulates production and secretory cargo trafficking of procollagen. We identify the C. elegans ortholog TMEM-39 from an unbiased RNAi screen and show that deficiency of tmem-39 leads to striking defects in cuticle collagen production and constitutively high ER stress response. RNAi knockdown of the tmem-39 ortholog in Drosophila causes similar defects in collagen secretion from fat body cells. The cytosolic domain of human TMEM39A binds to Sec23A, a vesicle coat protein that drives collagen secretion and vesicular trafficking. TMEM-39 regulation of collagen secretion is independent of ER stress response and autophagy. We propose that the roles of TMEM-39 in collagen secretion and ER homeostasis are likely evolutionarily conserved.

First Author:Zhe Zhang*

Correspondence Author:Dengke Ma*

All the Authors:Shuo Luo,Guilherme Oliveira Barbosa,Meirong Bai,Thomas B Kornberg

Indexed by:Article

Document Code:1

Impact Factor:5.54

DOI Number:10.1371/journal.pgen.1009317

Translation or Not:No

Date of Publication:2021-02

Included Journals:SCI

Links to Published Journals:https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009317

Release Time:2021-02-01