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.
NCBI Summary:
Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation.
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.
Expression regulated by
FSH, LH
Comment
Ovarian localization
Cumulus, Granulosa
Comment
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.