Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion

Abdallah Hamieh, Dorthe Cartier, Houssni Abid, André Calas, Carole Burel, Christine Bucharles, Cedric Jehan, Luca Grumolato, Marc Landry, Patrice Lerouge, Youssef Anouar, Isabelle Lihrmann

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Selenoprotein T (SelT) is a recently characterized thioredoxin-like protein whose expression is very high during development, but is confined to endocrine tissues in adulthood where its function is unknown. We report here that SelT is required for adaptation to the stressful conditions of high hormone level production in endocrine cells. Using immunofluorescence and TEM immunogold approaches, we find that SelT is expressed at the endoplasmic reticulum membrane in all hormone-producing pituitary cell types. SelT knockdown in corticotrope cells promotes unfolded protein response (UPR) and ER stress and lowers endoplasmic reticulum-associated protein degradation (ERAD) and hormone production. Using a screen in yeast for SelT-membrane protein interactions, we sort keratinocyte-associated protein 2 (KCP2), a subunit of the protein complex oligosaccharyltransferase (OST). In fact, SelT interacts not only with KCP2 but also with other subunits of the A-type OST complex which are depleted after SelT knockdown leading to POMC N-glycosylation defects. This study identifies SelT as a novel subunit of the A-type OST complex, indispensable for its integrity and for ER homeostasis, and exerting a pivotal adaptive function that allows endocrine cells to properly achieve the maturation and secretion of hormones.

Original languageEnglish
Pages (from-to)1935-1946
Number of pages12
JournalEMBO Reports
Volume18
Issue number11
DOIs
StatePublished - Nov 2017
Externally publishedYes

Keywords

  • ER stress
  • KCP2
  • N-glycosylation
  • oligosaccharyl transferase
  • pituitary

Fingerprint

Dive into the research topics of 'Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion'. Together they form a unique fingerprint.

Cite this