The syndecans are transmembrane heparan sulfate proteoglycans that appear to act as receptors or coreceptors involved
in intracellular communication. Syndecan-4 was isolated from rat endothelial cells, as ryudocan.
Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a
variable number of heparan sulfate chains. Two different cell surface heparan sulfate proteoglycan families can be
distinguished: (1) the syndecan-like integral membrane proteoglycans (SLIPS), with a core protein spanning the
cytoplasmic membrane, and (2) the glypican-related integral membrane proteoglycans (GRIPS), with a core protein
anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol.
Syndecan-4 was isolated from rat endothelial cells, as ryudocan.
NCBI Summary:
The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan that functions as a receptor in intracellular signaling. The encoded protein is found as a homodimer and is a member of the syndecan proteoglycan family. This gene is found on chromosome 20, while a pseudogene has been found on chromosome 22.
Sakata M, et al 2000 reported that ryudocan expression by luteinized granulosa cells is associated with the process of follicle atresia The follicular fluid (FF) and granulosa-lutein cells were aspirated from follicles 34 hours after an ovulatory gonadotropin bolus. Ryudocan was abundant in the FF. Atretic follicles had higher concentrations of ryudocan A detectable amount of ryudocan was found in pooled granulosa-lutein cells. Ryudocan production was augmented by surge levels of hCG. Thus, ryudocan is expressed in luteinized granulosa cells in vitro. The higher concentrations of ryudocan in FF of atretic follicles suggest an involvement of ryudocan in the process of atresia.
Expression regulated by
FSH, LH
Comment
Heparan Sulfate Proteoglycans Regulate Responses to Oocyte Paracrine Signals in Ovarian Follicle Morphogenesis. Watson LN et al. In the ovarian follicle, oocyte-secreted factors induce cumulus-specific genes and repress mural granulosa cell specific genes to establish these functionally distinct cell lineages. The mechanism establishing this precise morphogenic pattern of oocyte signaling within the follicle is unknown. The present study investigated a role for heparan sulphate proteoglycans (HSPG) as coreceptors mediating oocyte secreted factor signaling. In vitro maturation of cumulus oocyte complexes in the presence of exogenous heparin, which antagonizes HSPG signaling, prevented cumulus expansion and blocked the induction of cumulus-specific matrix genes, Has2 and Tnfaip6, whereas conversely, the mural granulosa-specific genes, Lhcgr and Cyp11a1, were strongly up-regulated. Heparin also blocked phosphorylation of SMAD2. Exogenous growth differentiation factor (GDF)-9 reversed these heparin effects; furthermore, GDF9 strongly bound to heparin sepharose. These observations indicate that heparin binds endogenous GDF9 and disrupts interaction with heparan sulphate proteoglycan coreceptor(s), important for GDF9 signaling. The expression of candidate HSPG coreceptors, Syndecan 1-4, Glypican 1-6, and Betaglycan, was examined. An ovulatory dose of human chorionic gonadotropin down-regulated Betaglycan in cumulus cells, and this regulation required GDF9 activity; conversely, Betaglycan was significantly increased in luteinizing mural granulosa cells. Human chorionic gonadotropin caused very strong induction of Syndecan 1 and Syndecan 4 in mural granulosa as well as cumulus cells. Glypican 1 was selectively induced in cumulus cells, and this expression appeared dependent on GDF9 action. These data suggest that HSPG play an essential role in GDF9 signaling and are involved in the patterning of oocyte signaling and cumulus cell function in the periovulatory follicle.
Ovarian localization
Cumulus, Granulosa
Comment
Cumulus cell gene expression is associated with oocyte developmental quality and influenced by patient and treatment characteristics. Adriaenssens T et al. BACKGROUND Gene expression of cumulus cells (CC) could predict oocyte developmental quality. Knowledge of the genes involved in determining oocyte quality is scanty. The aim was to correlate clinical and biological characteristics during ovarian stimulation with the expression of 10 selected genes in CC. METHODS Sixty-three ICSI patients were stimulated with GnRH-agonist plus highly purified hMG (n = 35) or recombinant FSH (n = 28). Thirteen variables were analyzed: Age, BMI, duration of stimulation, serum concentrations of progesterone, 17beta-estradiol, FSH and LH on day of hCG, Ovarian Response, Oocyte Maturity, 2 pronuclei and three embryo morphology related variables: >/=7 cells, Low Fragmentation, Good Quality Embryos score. Expression of HAS2, VCAN, SDC4, ALCAM, GREM1, PTGS1, PTGS2, DUSP16, SPROUTY4 and RPS6KA2 was analyzed in pooled CC using quantitative PCR, and the relationship to the 13 variables was evaluated by multivariable analysis. RESULTS All 10 genes are expressed at oocyte retrieval, with PTGS1, SPROUTY4, DUSP16 and RPS6KA2 described in human ovary for the first time. The three variables that correlated most often with differential expression were Age, BMI and serum FSH level. Significant correlation was found with Oocyte Maturity (VCAN, P < 0.005), Low Fragmentation (RPS6KA2, P < 0.05), Embryos with >/=7 cells (ALCAM and GREM1, P < 0.05). The expression of the other genes was also correlated to oocyte developmental quality but to a less extent. SDC4, VCAN, GREM1, SPROUTY4 and RPS6KA2 showed gonadotrophin preparation-dependent expression and/or interactions (all P < 0.05). CONCLUSION The expression of ovulation related genes in CC is associated with patient and treatment characteristics, oocyte developmental potential and differs with the type of gonadotrophin used.
Princivalle M, et al 2001 reported anticoagulant heparan sulfate proteoglycans expression in the rat ovary peaks in preovulatory granulosa cells.
Ovarian granulosa cells synthesize anticoagulant heparan sulfate proteoglycans (aHSPGs), which bind and activate antithrombin III. To determine if aHSPGs
could contribute to the control of proteolytic activities involved in
follicular development and ovulation, the authors studied the pattern of expression of these proteoglycans during the ovarian cycle. aHSPGs were localized on cells
and tissues by I-125-labeled antithrombin III binding followed by microscopic
autoradiography. Localization of aHSPCs has shown that cultured granulosa
cells, hormonally stimulated by gonadotropins to differentiate in vitro,
up-regulate their synthesis and release of aHSPGs. In vivo, during
gonadotropin-stimulated cycle, aHSPGs are present on granulosa cells of antral
follicles and are strongly labeled in preovulatory follicles. These data
demonstrate that aHSPG expression in the ovarian follicle is hormonally
induced to culminate in preovulatory follicles. Moreover, five heparan sulfate core proteins mRNA (perlecan; syndecan-1, -2, and -4; and
glypican-1) are synthesized by granulosa cells, providing attachment for
anticoagulant heparan sulfate chains on the cell surface and in the
extracellular matrix. These core proteins are constantly expressed during the
cycle, indicating that modulations of aHSPG levels observed in the ovary are
likely controlled at the level of the biosynthesis of anticoagulant heparan
sulfate glycosaminoglycan chains. This expression pattern enables aHSPGs to
focus serine protease inhibitors in the developing follicle to control
proteolysis and fibrin formation at ovulation.
Follicle stages
Antral, Preovulatory
Comment
Multiple signalling defects in the absence of RIP140 impair both cumulus expansion and follicle rupture Tullet JM, et al .
The expression of this gene was increased in the KO mice.