Transmembrane protein TMEM170A is a newly discovered regulator of ER and nuclear envelope morphogenesis in human cells

J Cell Sci. 2016 Apr 15;129(8):1552-65. doi: 10.1242/jcs.175273. Epub 2016 Feb 18.

Abstract

The mechanism of endoplasmic reticulum (ER) morphogenesis is incompletely understood. ER tubules are shaped by the reticulons (RTNs) and DP1/Yop1p family members, but the mechanism of ER sheet formation is much less clear. Here, we characterize TMEM170A, a human transmembrane protein, which localizes in ER and nuclear envelope membranes. Silencing or overexpressing TMEM170A in HeLa K cells alters ER shape and morphology. Ultrastructural analysis reveals that downregulation of TMEM170A specifically induces tubular ER formation, whereas overexpression of TMEM170A induces ER sheet formation, indicating that TMEM170A is a newly discovered ER-sheet-promoting protein. Additionally, downregulation of TMEM170A alters nuclear shape and size, decreases the density of nuclear pore complexes (NPCs) in the nuclear envelope and causes either a reduction in inner nuclear membrane (INM) proteins or their relocalization to the ER. TMEM170A interacts with RTN4, a member of the reticulon family; simultaneous co-silencing of TMEM170A and RTN4 rescues ER, NPC and nuclear-envelope-related phenotypes, implying that the two proteins have antagonistic effects on ER membrane organization, and nuclear envelope and NPC formation.

Keywords: Endoplasmic reticulum; Nuclear envelope; Nuclear pore complex; Reticulon; TMEM170A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / physiology*
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nogo Proteins / genetics
  • Nogo Proteins / metabolism*
  • Nuclear Envelope / metabolism*
  • Nuclear Pore / metabolism
  • Protein Transport / genetics
  • RNA, Small Interfering / genetics
  • Transgenes

Substances

  • Membrane Proteins
  • Nogo Proteins
  • RNA, Small Interfering
  • RTN4 protein, human
  • TMEM170A protein, human