U1242-OSS SPECIAL SEMINAR - Jérôme ARCHAMBAULT - Post-Doctoral Researcher - EPFL LAUZANNE - GHI – SV – Van der Goot Lab

TMEM214 : a new player in the regulation of ER morphology

Dr Jérôme ARCHAMBEAU

Post-Doctoral Researcher

EPFL LAUZANNE

GHI – SV – Van der Goot Lab

Abstract
The Endoplasmic Reticulum (ER) is the largest organelle in the cell and is responsible for many critical functions such as protein and lipid synthesis, as well as intracellular calcium regulation. The structural organization of the ER is highly dynamic and complex, comprising distinct subdomains such as the nuclear envelope, a dense perinuclear region enriched in sheets, and the peripheral ER, which is mostly organized into tubules. This organization is regulated by a set of proteins known as “shapers,” which are differentially localized within the ER. Climp63, p180, and Kinectin have been described to localize in ER sheets, whereas Reticulons, Reeps, Lunapark, and Atlastins stabilize the high membrane curvature characteristic of ER tubules.
We identified TMEM214 - a poorly characterized transmembrane protein - as a new regulator of ER morphology, since its depletion or overexpression alters the sheet-to-tubule ratio. We showed that this regulation might be mediated through the microtubule cytoskeleton. Indeed, TMEM214 not only associates with polymerized microtubules but also regulates their acetylation. Consistent with these phenotypes, TMEM214 depletion also disrupts the distribution of certain organelles, such as mitochondria and lysosomes, which become clustered in the perinuclear region in the absence of TMEM214. Our data further show that TMEM214 expression increases under ER stress conditions. RNA-seq and proteomic analyses suggest that TMEM214 is involved in the translation machinery by interacting with ribosomal proteins and regulating ribosome biogenesis.