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

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

Author information

1
Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
2
European Molecular Biology Laboratory, Heidelberg, Germany.
3
European Molecular Biology Laboratory, Heidelberg, Germany mattaj@embl.org.

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

PMID:
26906412
PMCID:
PMC4852765
DOI:
10.1242/jcs.175273
[Indexed for MEDLINE]
Free PMC Article

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