TRAILR3 contains a predicted signal sequence, 2 of the 4 cysteine-rich
pseudorepeats characteristic of the extracellular domain of members of the TNF receptor family, an
extracellular linker sequence, and a short, hydrophobic C-terminal sequence. Transient expression studies
showed that TRAILR3 is a plasma membrane-bound protein capable of high affinity interaction with the
TRAIL ligand. In contrast to TRAILR1 and TRAILR2, TRAILR3 appears to be
glycosylphosphatidylinositol-linked and lacks a cytoplasmic region, including the death domain. TRAILR3 acts as an inhibitor of TRAIL-mediated apoptosis by
competing with the other TRAIL receptors for binding to the ligand.
NCBI Summary:
The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL.
General function
Receptor, Cell death/survival, Anti-apoptotic
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Follicle atresia
Comment
Wada S, et al 2002 reported that
TRAIL-decoy receptor 1 plays inhibitory role in apoptosis of
granulosa cells from pig ovarian follicles.
Previously, the authors histochemically examined the localization of tumor necrosis
factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its receptors in
porcine ovarian follicles. and demonstrated a marked reduction in the
expression of TRAIL-decoy receptor-1 (DcR1) in granulosa cells of atretic
follicles. In the present study, to confirm the inhibitory activity of DcR1 in
granulosa cells, granulosa cells prepared from healthy follicles were treated
with phosphatidylinositol-specific phospholipase C (PI-PLC) to cleave
glycophospholipid anchor of DcR1 and to remove DcR1 from the cell surface, and
then incubated with TRAIL, PI-PLC treatment increased the number of apoptotic
cells induced by TRAIL. The present finding indicated the possibility that
TRAIL and its receptors were involved in induction of apoptosis in granulosa
cells during atresia, and that DcR1 plays an inhibitory role in granulosa cell
apoptosis.
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
Comment
TRAIL pathway components and their putative role in granulosa cell apoptosis in the human ovary. Jskelinen M et al. Extensive apoptotic oocyte reduction occurs during fetal ovarian development. The regulatory pathways responsible for oocyte selection to programmed cell death are, however, poorly understood. The aim of this study was to investigate the potential involvement of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5 and decoy receptors TRAIL-R3/DcR1 and TRAIL-R4/DcR2 in the apoptotic process characterizing human fetal and adult ovaries. For this purpose, in situ hybridization and immunohistochemistry were applied to human fetal and adult ovarian samples to study the mRNA and protein expression of TRAIL pathway components, and a human granulosa cell tumor-derived cell line (KGN) was used to elucidate functional effects of TRAIL on apoptosis. TRAIL was expressed in human fetal ovary from the 11th week until term. The pro-apoptotic TRAIL-R2/DR5 and the anti-apoptotic TRAIL-R4/DcR2 were also expressed in human ovaries throughout the fetal period. Among the different ovarian cell types, these TRAIL pathway components were mainly localized in the oocytes, and their expression increased towards term. Expression of TRAIL-R1/DR4 and TRAIL-R3/DcR1 was negligible in all of the fetal ovaries studied. Adult ovaries expressed TRAIL, TRAIL-R2/DR5, TRAIL-R3/DcR1 and TRAIL-R4/DcR2 in granulosa cells and oocytes of small primary/secondary follicles as well as in granulosa and theca cells of more developed antral follicles. In KGN cells, TRAIL efficiently induced apoptosis in a dose-dependent manner, and this was blocked by a caspase inhibitor. The results indicate a role of the TRAIL pathway components in the regulation of granulosa cell apoptosis in in vitro and suggest that these factors may have a role in regulating ovarian apoptosis also in vivo.