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

Autor: Zhang Z; School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America., Luo S; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America., Barbosa GO; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America., Bai M; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America., Kornberg TB; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America.; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America., Ma DK; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America.; Department of Physiology, University of California San Francisco, San Francisco, California, United States of America.; Innovative Genomics Institute, Berkeley, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2021 Feb 01; Vol. 17 (2), pp. e1009317. Date of Electronic Publication: 2021 Feb 01 (Print Publication: 2021).
DOI: 10.1371/journal.pgen.1009317
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje