A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways

Kuriyama, Sei; Mayor, Roberto

doi:10.1242/dev.027334

Cited by 41 publications

(35 citation statements)

References 86 publications

(136 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies on HSPG-mediated signaling have focused on syndecan-4, a transmembrane HSPG with its cytoplasmic domain capable of activating and stabilizing PKCα, and syndecan-4-dependent PKCα activation has been indicated in fibroblast growth factor signaling. 39,40 Moreover, neuronal Thy-1-induced cell spreading requires RhoA-mediated actin cytoskeleton polymerization, a suggested downstream event after syndecan-4-dependent PKCα activation. 41 Our study also indicated that the RhoA activation induced by latent heparanase is mediated by PKCα.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Heparanase Regulates Heart Metabolism by Stimulating Lipoprotein Lipase Secretion From Cardiomyocytes

Wang

Zhang²,

Chiu³

et al. 2013

ATVB

View full text Add to dashboard Cite

A fter diabetes mellitus, the heart has an increased reliance on fatty acids (FAs) for generation of energy.1 The majority of these FAs come from breakdown of circulating triglyceride-rich lipoproteins, a process catalyzed by lipoprotein lipase (LPL) located at the luminal side of vascular endothelial cells (ECs).2-4 ECs do not express LPL. In the heart, LPL is synthesized in cardiomyocytes and secreted to ECs. 5 We have previously reported an increase of coronary LPL in animal models of type 1 diabetes mellitus, an effect that was evident in the absence of any change in myocyte LPL gene expression. 6,7 We concluded that the augmented coronary LPL was a result of increased secretion of the enzyme from myocytes toward the coronary lumen. Regarding secretion, LPL is first transported from an intracellular pool in the myocyte to the cell surface, where it binds to heparan sulfate proteoglycans (HSPGs). 8 We have shown that this intracellular transport depends on actin cytoskeleton polymerization, a process that is magnified after diabetes mellitus.9,10 The subsequent process by which myocyte surface LPL is translocated to the coronary lumen, in addition to its replenishment after this onward movement, has not been completely elucidated.Myocyte surface HSPGs serve as a temporary docking site and an auxiliary reservoir of LPL. HSPGs are proteoglycans bearing HS side chains attached to specific serine residues of a protein core.11 Core proteins can be attached to the cell surface through a glycosylphosphatidyl inositol anchor in case of glypican, or can traverse the membrane as observed with the syndecan family.12,13 The HS side chains are polymers of repeating disaccharides which interact with multiple ligands, including antithrombin, fibroblast growth factor, and LPL. Objective-After diabetes mellitus, transfer of lipoprotein lipase (LPL) from cardiomyocytes to the coronary lumen increases, and this requires liberation of LPL from the myocyte surface heparan sulfate proteoglycans with subsequent replenishment of this reservoir. At the lumen, LPL breaks down triglyceride to meet the increased demand of the heart for fatty acid. Here, we examined the contribution of coronary endothelial cells (ECs) toward regulation of cardiomyocyte LPL secretion. Approach and Results-Bovine coronary artery ECs were exposed to high glucose, and the conditioned medium was used to treat cardiomyocytes. EC-conditioned medium liberated LPL from the myocyte surface, in addition to facilitating its replenishment. This effect was attributed to the increased heparanase content in EC-conditioned medium. Of the 2 forms of heparanase secreted from EC in response to high glucose, active heparanase released LPL from the myocyte surface, whereas latent heparanase stimulated reloading of LPL from an intracellular pool via heparan sulfate proteoglycanmediated RhoA activation. Conclusions-Endothelial heparanase is a participant in facilitating LPL increase at the coronary lumen. These observations provide an insight into the cross-talk between ECs ...

show abstract

Section: Discussionmentioning

confidence: 99%

Endothelial Heparanase Regulates Heart Metabolism by Stimulating Lipoprotein Lipase Secretion From Cardiomyocytes

Wang

Zhang²,

Chiu³

et al. 2013

ATVB

View full text Add to dashboard Cite

show abstract

“…In Xenopus, the transmembrane proteoglycan Sdc4 is co-expressed with PN1 in the early animal hemisphere of blastula and anterior neural plate of neurula embryos (Muñoz et al, 2006;Kuriyama and Mayor, 2009). Moreover, Sdc4 is a proteolytic target of HtrA1 (Hou et al, 2007).…”

Section: Pn1 Stabilizes Sdc4 Against Degradation By Htra1mentioning

confidence: 99%

The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation

et al. 2015

View full text Add to dashboard Cite

Germ layer formation and primary axis development rely on Fibroblast growth factors (FGFs). In Xenopus, the secreted serine protease HtrA1 induces mesoderm and posterior trunk/tail structures by facilitating the spread of FGF signals. Here, we show that the serpin Protease nexin-1 (PN1) is transcriptionally activated by FGF signals, suppresses mesoderm and promotes head development in mRNAinjected embryos. An antisense morpholino oligonucleotide against PN1 has the opposite effect and inhibits ectodermal fate. However, ectoderm and anterior head structures can be restored in PN1-depleted embryos when HtrA1 and FGF receptor activities are diminished, indicating that FGF signals negatively regulate their formation. We show that PN1 binds to and inhibits HtrA1, prevents degradation of the proteoglycan Syndecan 4 and restricts paracrine FGF/Erk signaling. Our data suggest that PN1 is a negative-feedback regulator of FGF signaling and has important roles in ectoderm and head development.

show abstract

“…SDC4 is highly complex by virtue of its external side chains, and thus interacts with a variety of ligands, such as vascular endothelial growth factors (VEGFs), platelet-derived growth factors (PDGFs) and fibroblast growth factors (FGFs) (4). At the cell membrane, SDC4 stabilizes the interactions between ligands and receptors by forming a ternary complex, which has been demonstrated in several signaling pathways (5,6). Proteolytic cleavage and shedding of its extracellular domain can spread FGF signaling to adjacent cells, thus regulating the local reception of FGF signaling activity (7).…”

Section: Introductionmentioning

confidence: 99%

Expression and roles of syndecan-4 in dental epithelial cell differentiation

Zhang

Yang

Sun

et al. 2014

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Syndecan-4 (SDC4), a transmembrane heparan sulfate proteoglycan, acts as a signal transducer. It affects the growth and differentiation of a number of tissues and organs. However, the specific mechanisms through which SDC4 regulates the differentiation of dental epithelial cells (amelogenesis) and tooth development remains largely unknown. In the present study, to identify the SDC4-regulated processes in dental epithelial cells, the SDC4 expression pattern was examined in mouse molar and postnatal incisor tooth germs during the late bell stage of development. Small interfering RNA (siRNA) was designed for this study and used to downregulate SDC4 expression in the rat dental epithelial cell line, HAT-7. The results revealed that SDC4 was mainly present in the oral epithelium, the dental epithelial cells of enamel organs in the molars and the cervical loops in the incisors. When the inner enamel epithelial cells gave rise to ameloblasts, however, the loss of SDC4 expression was evident. SDC4 was also expressed in stratum intermedium (SI) cells in the incisors and in dental mesenchymal cells adjacent to the cervical loops in molars (E18) and postnatal incisors. Fibroblast growth factor 10 (FGF10) promoted proliferation and slightly decreased cell differentiation. The knockdown of SDC4 using specific siRNA led to a decrease in cell proliferation and a highly significant increase in amelogenin, ameloblastin, kallikrein 4 and matrix metalloproteinase 20 expression, molecules that are known to participate in the formation of enamel. These effects were attenuated by FGF10, which upregulated SDC4 expression. Taken together, these results suggest that SDC4 participates in amelogenesis, and FGF10 may modulate dental epithelial cell behaviors through the regulation of SDC4 expression. IntroductionSyndecan (SDC)4 is a cell surface heparan sulfate proteoglycan (HSPG). Its heparan sulfate (HS) chains and core protein could control the stability, movement and reception of diffusible heparin-binding growth factors (1). In addition, it can form physical connections between the extracellular matrix (ECM) and intracellular signaling to affect the growth and differentiation of a number of tissues and organs (2,3). SDC4 is highly complex by virtue of its external side chains, and thus interacts with a variety of ligands, such as vascular endothelial growth factors (VEGFs), platelet-derived growth factors (PDGFs) and fibroblast growth factors (FGFs) (4). At the cell membrane, SDC4 stabilizes the interactions between ligands and receptors by forming a ternary complex, which has been demonstrated in several signaling pathways (5,6). Proteolytic cleavage and shedding of its extracellular domain can spread FGF signaling to adjacent cells, thus regulating the local reception of FGF signaling activity (7). Its cytoplasmic domains can also initiate FGF-induced signaling independently of FGFRs through the activation of Rho GTPases, such as Rac1, which plays an essential role in the dental epithelium, involving cell-matrix interactio...

show abstract

A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways

Cited by 41 publications

References 86 publications

Endothelial Heparanase Regulates Heart Metabolism by Stimulating Lipoprotein Lipase Secretion From Cardiomyocytes

Endothelial Heparanase Regulates Heart Metabolism by Stimulating Lipoprotein Lipase Secretion From Cardiomyocytes

The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation

Expression and roles of syndecan-4 in dental epithelial cell differentiation

Contact Info

Product

Resources

About