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

被引:23
作者
Christodoulou, Andri [1 ]
Santarella-Mellwig, Rachel [2 ]
Santama, Niovi [1 ]
Mattaj, Iain W. [2 ]
机构
[1] Univ Cyprus, Dept Biol Sci, Nicosia, Cyprus
[2] European Mol Biol Lab, Heidelberg, Germany
关键词
TMEM170A; Reticulon; Endoplasmic reticulum; Nuclear envelope; Nuclear pore complex; TUBULAR ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; MAMMALIAN-CELLS; PORE; NETWORK; TRANSFORMATION; MORPHOLOGY; CURVATURE; CISTERNAE; DYNAMICS;
D O I
10.1242/jcs.175273
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1552 / 1565
页数:14
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