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

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...

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Published in:PLoS genetics 2021-02, Vol.17 (2), p.e1009317-e1009317
Main Authors: Zhang, Zhe, Luo, Shuo, Barbosa, Guilherme Oliveira, Bai, Meirong, Kornberg, Thomas B, Ma, Dengke K
Format: Article
Language:English
Subjects:
Animals
Biology and life sciences
Cell death
Cellular stress response
Collagen
CRISPR
Electron microscopy
Gel electrophoresis
Genes
Genomes
Heat shock proteins
Histones
Microscopy
Morphology
Mutants
Phenotypes
Physical Sciences
Protein folding
Proteins
Research and Analysis Methods
RNA-mediated interference
Secretion
Sodium lauryl sulfate
Transcription
Transmembrane proteins
Worms
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description 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.
doi_str_mv 10.1371/JOURNAL.PGEN.1009317
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source PubMed (Medline); Access via ProQuest (Open Access); Coronavirus Research Database
subjects Animals
Biology and life sciences
Cell death
Cellular stress response
Collagen
CRISPR
Electron microscopy
Gel electrophoresis
Genes
Genomes
Heat shock proteins
Histones
Microscopy
Morphology
Mutants
Phenotypes
Physical Sciences
Protein folding
Proteins
Research and Analysis Methods
RNA-mediated interference
Secretion
Sodium lauryl sulfate
Transcription
Transmembrane proteins
Worms
title The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response
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