Glypicans

Filmus, Jorge; Capurro, Mariana; Rast, Jonathan P.

doi:10.1186/gb-2008-9-5-224

Cited by 535 publications

(538 citation statements)

References 31 publications

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“…Cell surface HSPGs, e.g. of the syndecan or glypican families (Alexopoulou et al, 2007;Filmus et al, 2008), mediate cell-cell and cellmatrix contacts and function as co-receptors for various growth factors (Mythreye and Blobe, 2009). In addition, cell surface HSPGs lining the vascular endothelium act as sites for leukocyte attachment, thereby facilitating migration of blood-borne cells into tissues (Wang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

Waern

Jia

Pejler

et al. 2010

Molecular Immunology

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Heparanase is a heparan sulfate (HS) degrading endoglucuronidase that has been implicated in cell migration and inflammatory conditions. Here we used mice deficient of heparanase (Hpse -/-) to study the impact of heparanase on airway leukocytes. Normal numbers of macrophages and lymphocytes were present in bronchoalveolar lavage fluid of Hpse-/-mice, indicating that heparanase is not essential for proper homing of leukocytes to airways. While lymphocytes fromHpse -/-mice displayed normal morphology, Hpse -/-alveolar macrophages showed a striking, age-dependent appearance of granule-like structures in the cytoplasm.Transmission electron microscopy revealed that these structures corresponded to membrane-enclosed crystalline bodies that closely resembled the intracellular crystals known to be formed by the HS-binding protein Ym1, suggesting that heparanase deficiency is associated with intracellular Ym1 deposition. Indeed, applying immunocytochemistry, we found markedly higher levels of intracellular

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Section: Introductionmentioning

confidence: 99%

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

Waern

Jia

Pejler

et al. 2010

Molecular Immunology

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“…However, not much is known until now about a possible association of Glypican-1 with kidney disease. While in humans only six different Gypican proteins exist [7], in zebrafish ten different Glypican proteins have been isolated [8]. In contrast to humans, in zebrafish two different isoforms of Glypican-1, named Glypican-1a and 1b, and three different isoforms of Glypican 5, named Glypican-5a, 5b and 5c, have been identified 8.…”

Section: Introductionmentioning

confidence: 99%

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

Stahl¹,

Hegermann²,

Njau³

et al. 2017

Nephrol Renal Dis

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Components of the glycocalyx are being intensively studied for their involvement in a vast array of glomerular diseases. Among the most abundant proteoglycans in the glomerular cell glycocalyx are the heparan sulfate proteoglycans Glypican-1 and 5, expressed predominantly in glomerular endothelial and epithelial cells, respectively.We used a previously characterized zebrafish model to define the role of all different in zebrafish existing isoforms of Glypican-1 (a and b) and 5 (a,b and c) in vascular and renal pathology and tested the hypothesis that Glypican expression is important for the integrity of the glomerular barrier. Glypican morpholino knockdown in l-fabp:DBP-eGFP fish showed edematous phenotypes and a significant reduction of eye fluorescence for Glypican-1a, 5a und 5c, but not for Glypican1b and 5b isoforms. This indicates a significant loss of plasma proteins following knockdown of Glypican-1a, 5a and 5c in contrast to a conserved filtration barrier following knockdown of Glypican-1b and 5b isoforms. Knockdown of all different examined Glypican isoforms did not interfere with early nephron development as shown in the WT1b fish strain. Using electron microscopy, we could demonstrate that Glypican-1a knockdown leads to a predominantly endothelial cell injury with preservation of podocyte foot processes, while knockdown of Glypicans-5a and 5c shows focal podocyte effacement with conserved endothelial structures. Ultrastructural analysis of glomeruli following knockdown of Glypicans-1b and 5b reveals normal glomerular structure.In this brief study we demonstrate in an in-vivo model that the Glypican proteoglycan family is critical in vascular and glomerular integrity. Our observations suggest a role for Glypican-1a in endothelial cell and Glypican-5a and 5b in podocyte cell injury leading to subsequent loss of glomerular filtration barrier function and proteinuria.

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“…This processing appears required for some but not all glypican activity (2,3). The stalk regions of glypicans are predicted to be largely random coil and typically contain 1-5 heparan sulfate attachment sites (1,4). Six glypicans are present in humans and mice (glypican-1, -2, -3, -4, -5, and -6); two are present in Drosophila [Dally and Dally-like (Dlp)] (1).…”

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confidence: 99%

“…Six glypicans are present in humans and mice (glypican-1, -2, -3, -4, -5, and -6); two are present in Drosophila [Dally and Dally-like (Dlp)] (1). Based on sequence similarity, glypicans assort into two subfamilies with glypican-1, -2, -4, -6, and Dlp in one family and glypican-3, -5, and Dally in another (1).…”

mentioning

confidence: 99%

“…G lypicans are heparan sulfate proteoglycans (HSPGs) that consist of an approximately 450 amino acid N-terminal protein domain followed by an approximately 100 amino acid stalk region that is attached to the outer cell membrane via a glycosylphosphatidylinositol anchor (1). The N-terminal domain of most glypicans is proteolytically processed by a furin-like convertase to produce two chains that remain connected by disulfide bonds (2).…”

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confidence: 99%

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Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling

Kim

Saunders

Hamaoka

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Glypicans are heparan sulfate proteoglycans that modulate the signaling of multiple growth factors active during animal development, and loss of glypican function is associated with widespread developmental abnormalities. Glypicans consist of a conserved, approximately 45-kDa N-terminal protein core region followed by a stalk region that is tethered to the cell membrane by a glycosyl-phosphatidylinositol anchor. The stalk regions are predicted to be random coil but contain a variable number of attachment sites for heparan sulfate chains. Both the N-terminal protein core and the heparan sulfate attachments are important for glypican function. We report here the 2.4-Å crystal structure of the N-terminal protein core region of the Drosophila glypican Dally-like (Dlp). This structure reveals an elongated, α-helical fold for glypican core regions that does not appear homologous to any known structure. The Dlp core protein is required for normal responsiveness to Hedgehog (Hh) signals, and we identify a localized region on the Dlp surface important for mediating its function in Hh signaling. Purified Dlp protein core does not, however, interact appreciably with either Hh or an Hh:Ihog complex.

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Glypicans

Abstract: The glypican family of cell-surface heparan sulfate proteoglycans modulate the actions of many developmentally important signal proteins.

Cited by 535 publications

References 31 publications

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

Accumulation of Ym1 and formation of intracellular crystalline bodies in alveolar macrophages lacking heparanase

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

Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling

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