Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone secretion
EMBO Rep. 2017-09-19; 18(11): 1935-1946
DOI: 10.15252/embr.201643504
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1. EMBO Rep. 2017 Nov;18(11):1935-1946. doi: 10.15252/embr.201643504. Epub 2017 Sep
19.
Selenoprotein T is a novel OST subunit that regulates UPR signaling and hormone
secretion.
Hamieh A(1)(2), Cartier D(1)(2), Abid H(1)(2), Calas A(3), Burel C(2)(4),
Bucharles C(1)(2), Jehan C(1)(2), Grumolato L(1)(2), Landry M(3), Lerouge
P(2)(4), Anouar Y(1)(2), Lihrmann I(5)(2).
Author information:
(1)Neuronal and Neuroendocrine Differentiation and Communication Laboratory,
Rouen-Normandie University UNIROUEN, Inserm, U1239, Mont-Saint-Aignan, France.
(2)Institute for Research and Innovation in Biomedicine, Rouen, France.
(3)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of
Bordeaux, Bordeaux, France.
(4)Glyco-MEV Laboratory, Rouen-Normandie University UNIROUEN, Mont-Saint-Aignan,
France.
(5)Neuronal and Neuroendocrine Differentiation and Communication Laboratory,
Rouen-Normandie University UNIROUEN, Inserm, U1239, Mont-Saint-Aignan, France
.
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.
© 2017 The Authors.
DOI: 10.15252/embr.201643504
PMCID: PMC5666612
PMID: 28928140 [Indexed for MEDLINE]