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

Autoři: Zhe Zhang aff001;  Shuo Luo aff002;  Guilherme Oliveira Barbosa aff002;  Meirong Bai aff002;  Thomas B. Kornberg aff002;  Dengke K. Ma aff002
Působiště autorů: School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China aff001;  Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America aff002;  Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America aff003;  Department of Physiology, University of California San Francisco, San Francisco, California, United States of America aff004;  Innovative Genomics Institute, Berkeley, California, United States of America aff005
Vyšlo v časopise: The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response. PLoS Genet 17(2): e1009317. doi:10.1371/journal.pgen.1009317
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009317


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.

Klíčová slova:

Caenorhabditis elegans – Collagens – Endoplasmic reticulum stress response – Fluorescence imaging – Monomers – Protein secretion – RNA interference – Secretion


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