Transmembrane protein TMEM170A is a novel regulator of ER and NE 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 NE membranes. Silencing or overexpressing TMEM170A in HeLa K cells alters ER shape and morphology. Ultrastructural analysis reveals that down-regulation of TMEM170A specifically induces tubular ER formation, while overexpression of TMEM170A induces ER sheet formation, indicating that TMEM170A is a novel ER sheet-promoting protein. Additionally, down-regulation of TMEM170A alters nuclear shape and size, decreases the density of nuclear pore complexes (NPCs) in the NE 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 NE-related phenotypes, implying that the two proteins have antagonistic effects on ER membrane organization, NE and NPC formation.