TMCO1 is essential for ovarian follicle development by regulating ER Ca2+ store of granulosa cells.

Cell Death and Differentiation
Zhongshuai SunTie-Shan Tang

Abstract

TMCO1 (transmembrane and coiled-coil domains 1) is an endoplasmic reticulum (ER) transmembrane protein that actively prevents Ca2+ stores from overfilling. To characterize its physiological function(s), we generated Tmco1-/- knockout (KO) mice. In addition to the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, Tmco1-/- females manifest gradual loss of ovarian follicles, impaired ovarian follicle development, and subfertility with a phenotype analogous to the premature ovarian failure (POF) in women. In line with the role of TMCO1 as a Ca2+ load-activated Ca2+ channel, we have detected a supernormal Ca2+ signaling in Tmco1-/- granulosa cells (GCs). Interestingly, although spontaneous Ca2+ oscillation pattern was altered, ER Ca2+ stores of germinal vesicle (GV) stage oocytes and metaphase II (MII) arrested eggs were normal upon Tmco1 ablation. Combined with RNA-sequencing analysis, we also detected increased ER stress-mediated apoptosis and enhanced reactive oxygen species (ROS) level in Tmco1-/- GCs, indicating the dysfunctions of GCs upon TMCO1 deficiency. Taken together, these results reveal that TMCO1 is essential for ovarian follicle development and female fertility by maintaining ER Ca2+ homeo...Continue Reading

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Apr 9, 2019·The Journal of Endocrinology·Madeleine R Di NataleLuba Sominsky
Jun 28, 2020·Molecular Reproduction and Development·Takane KanekoHiroshi Iida
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Datasets Mentioned

BETA
CRA000296

Methods Mentioned

BETA
PCR
RNA-seq
flow cytometry
biopsies
genotyping
light microscopy
Assay

Software Mentioned

Excel
Prism
IPA
GraphPad Prism
edgeR
Tophat
GraphPad
Metamorph

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