Transmembrane protein 208: a novel ER-localized protein that regulates autophagy and ER stress

PLoS One. 2013 May 14;8(5):e64228. doi: 10.1371/journal.pone.0064228. Print 2013.

Abstract

Autophagy and endoplasmic reticulum (ER) stress are both tightly regulated cellular processes that play central roles in various physiological and pathological conditions. Recent reports have indicated that ER stress is a potent inducer of autophagy. However, little is known about the underlying molecular link between the two processes. Here we report a novel human protein, transmembrane protein 208 (TMEM208) that can regulate both autophagy and ER stress. When overexpressed, TMEM208 impaired autophagy as characterized by the decrease of the accumulation of LC3-II, decreased degradation of autophagic substrates, and reduced expression of critical effectors and vital molecules of the ER stress and autophagy processes. In contrast, knockdown of the TMEM208 gene promoted autophagy, as demonstrated by the increase of LC3-II, increased degradation of autophagic substrates, and enhanced expression levels for genes key in the ER stress and autophagic processes. Taken together, our results reveal that this novel ER-located protein regulates both ER stress and autophagy, and represents a possible link between the two different cellular processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autophagy*
  • Base Sequence
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Stress*
  • Gene Expression Regulation
  • Hot Temperature
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Protein Transport

Substances

  • Membrane Proteins
  • TMEM208 protein, human

Grant support

This work was supported by a grant from the National Key Basic Research Program of China (973 Program, 2011CB910103). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.