Expression of the Cell Surface Proteoglycan Glypican-5 Is Developmentally Regulated in Kidney, Limb, and Brain

Abstract

Heparan sulfate is ubiquitous at the cell surface, where it is expressed predominantly on proteoglycans of either the transmembrane syndecan family or the glycosylphosphatidylinositol (GPI)-anchored glypican family, and has been proposed to function as a "coreceptor" for a number of "heparin-binding" growth factors. Although little is known about functional differences between individual members of the glypican gene family, mutations in both the Drosophila gene dally and the human gene for glypican-3 strongly suggest that at least some glypicans do function in cellular growth control and morphogenesis. In particular, deletion of the human glypican-3 gene is responsible for Simpson-Golabi-Behmel syndrome, and its associated pre- and postnatal tissue overgrowth, increased risk of embryonal tumors during early childhood, and numerous visceral and skeletal anomalies. We have identified and characterized, by sequencing of EST clones and products of rapid amplification of cDNA ends (RACE), an mRNA that encodes a 572-amino-acid member of the glypican gene family (glypican-5) that is most related (50% amino acid similarity, 39% identity) to glypican-3. Glypican-5 mRNA is detected as a 3.9- and 4.4-kb transcript in adult and neonatal mouse brain total RNA, and in situ hybridization results localize transcript primarily to restricted regions of the developing central nervous system, limb, and kidney in patterns consistent with a role in the control of cell growth or differentiation. Interestingly, glypican-5 localizes to 13q31-32 of the human genome, deletions of which are associated with human 13q- syndrome, a developmental disorder with a pattern of defects that shows significant overlap with the pattern of glypican-5 expression.

Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage

“…Soluble guanylate cyclase 1␣3 subunit (GUCY1A3; 8.17-fold) functions as the main receptor for nitric oxide. Glypican 5 (GPC5; 4.82-fold) is a glycosyl phosphatidylinositol (GPI)-anchored heparan sulfate proteoglycan and functions as a "coreceptor" for several "heparin-binding" growth factors (11). Apolipoprotein D (APOD; 6.24-fold) is a member of the lipocalin superfamily of transporter proteins that bind progesterone and arachidonic acid (12).…”

Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma

“…Saunders et al (11) investigated the expression levels of GPC5 in different embryonic and adult tissues. The authors of that study demonstrated that GPC5 is expressed in almost all embryonic tissues and this expression is maintained and even increased in adult brains, whereas in all other adult tissues, including the gastric epithelium, this expression is markedly suppressed to trace levels.…”

“…Glypicans are predominantly expressed during development and it has been demonstrated that expression levels vary in a spatiotemporal manner, suggesting that glypicans are involved in morphogenesis (10,11). In addition, it has been clearly established that glypicans are required for the optimal activity of heparin-binding factors, including fibroblast growth factors (FGFs) and Wnt (12,13).…”

Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma

“…This signaling pathway may be of particular relevance to neuroblastoma cells because they arise from migratory neural crest-derived neuroblasts (11)(12)(13). Glypicans play an important role in developmental morphogenesis and are known to be modulators for the Wnt signaling pathway (14)(15)(16)(17). It has been shown that GPC3, another member of the glypican family, may function as a coreceptor for Wnt and facilitate the Wnt/Frizzled binding in hepatocellular carcinoma cells (18,19).…”