title: Transmembrane protein TMEM170A is a newly discovered regulator of ER and nuclear envelope morphogenesis in human cells.
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.
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
authors.forename: Andri
authors.initials: A
authors.lastname: Christodoulou
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Rachel
authors.initials: R
authors.lastname: Santarella-Mellwig
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
authors.forename: Niovi
authors.initials: N
authors.lastname: Santama
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany mattaj@embl.org.
authors.forename: Iain W
authors.identifier: http://orcid.org/0000-0002-5537-8284
authors.initials: IW
authors.lastname: Mattaj
mesh_terms: D004721:Endoplasmic Reticulum / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000070798:Nogo Proteins / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D022022:Nuclear Pore / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D019076:Transgenes
chemical_list: D008565:Membrane Proteins; D000070798:Nogo Proteins; D034741:RNA, Small Interfering; C000603199:RTN4 protein, human; C582577:TMEM170A protein, human
keywords: Endoplasmic reticulum; Nuclear envelope; Nuclear pore complex; Reticulon; TMEM170A