Expression of the heparan sulfate proteoglycan glypican‐1 in the developing rodent

Abstract

The glypicans are a family of glycosylphosphatidylinositol (GPI)-anchored proteoglycans that, by virtue of their cell-surface localization and possession of heparan sulfate chains, may regulate the responses of cells to numerous heparin-binding growth factors, cell adhesion molecules, and extracellular matrix components. Mutations in one glypican cause a syndrome of human birth defects, suggesting important roles for these proteoglycans in development. Glypican-1, the first-discovered member of this family, was originally found in cultured fibroblasts, and later shown to be a major proteoglycan of the mature and developing brain. Here we examine the pattern of glypican-1 mRNA and protein expression more widely in the developing rodent, concentrating on late embryonic and early postnatal stages. High levels of glypican-1 expression were found throughout the brain and skeletal system. In the brain, glypican-1 mRNA was widely, and sometimes only transiently, expressed by zones of neurons and neuroepithelia. Glypican-1 protein localized strongly to axons and, in the adult, to synaptic terminal fields as well. In the developing skeletal system, glypican-1 was found in the periosteum and bony trabeculae in a pattern consistent with expression by osteoblasts, as well as in the bone marrow. Glypican-1 was also observed in skeletal and smooth muscle, epidermis, and in the developing tubules and glomeruli of the kidney. Little or no expression was observed in the developing heart, lung, liver, dermis, or vascular endothelium at the stages examined. The tissue-, cell type-, and in some cases stage-specific expression of glypican-1 revealed in this study are likely to provide insight into the functions of this proteoglycan in development.

Heparan Sulfate Regulates Targeting of Syndecan-1 to a Functional Domain on the Cell Surface

“…Antibodies and Reagents-The following monoclonal antibodies were used: FITC-labeled mouse anti-human syndecan-1 (CD138) antibody (clone BB4, Serotec, Oxford, UK) (17); FITC-labeled rat anti-mouse syndecan-1 antibody (clone 281.2) (18); biotinylated anti-human ICAM-1 (CD54) (clone HA58, BD Biosciences); rabbit anti-rat glypican-1 polyclonal antibody (kindly provided by Dr. Arthur Lander) (19); and anti-heparan sulfate antibody (clone 10E4, Seikagaku America, Falmouth, MA) (20). Triton X-100, cholera toxin beta-FITC, cytochalasin-D, and heparin isolated from porcine intestinal mucosa were purchased from Sigma.…”

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).…”

Knockdown of Glypican-1 and 5 isoforms causes proteinuria and glomerular injury in zebrafish (Danio rerio)

“…Given the fact that Glypican-1is expressed in both glomerular endothelial cells and in podocytes [3,16], we proceeded to investigate which cell type might be primary responsible for the disruption of glomerular filter integrity following Glypican knockdown in the zebrafish model. Our experiments provide further evidence that Glypican-1 gene knockdown leads to a predominant endothelial injury, while Glypican5a and 5c results in a podocyte phenotype.…”

“…Of the diverse Glypican proteoglycan family Glypicans-1, 3, 4 and 5 are found in the human kidney. [3][4][5]. Recently, Okamoto et.…”