Proteoglycan and glycosaminoglycan synthesis in embryonic mouse salivary glands: effects of beta-D-xyloside, an inhibitor of branching morphogenesis.

Thompson, Holly; Spooner, Brian S.

doi:10.1083/jcb.96.5.1443

Cited by 100 publications

(43 citation statements)

References 35 publications

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“…This shift with xylosides, although 1092 THE JOURNAL OF CELt BIOLOGY . VOLUME 101, 1985 not universal (11), has been observed previously (40). Although heparan and chondroitin sulfates share the same trisaccharide linkage to core protein (19), subsequent elongation depends on different specific enzymes.…”

Section: Discussionmentioning

confidence: 92%

Glycosaminoglycan synthesis is depressed during mitosis and elevated during early G1.

Preston¹,

Regula²,

Sager³

et al. 1985

The Journal of Cell Biology

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[35S]Sulfate incorporation was measured in populations of Chinese hamster ovary cells enriched for mitotics, early G1 cells, and interphase monolayers or suspensions. Incorporation was determined by biochemical analysis of extracts and quantitative autoradiography of thick sections. 90% of [35S]sulfate was incorporated into glycosaminoglycan (GAG). Incorporation was depressed fourfold in mitotics and stimulated by from two-to three-fold in early G1 cells relative to mixed interphase cells. GAG synthesis was maintained into late G2. Thus, the rate of GAG biosynthesis was correlated temporally with the detachment and reattachment of cells to substrate.Inhibitors of protein synthesis brought about the rapid arrest of GAG biosynthesis. However, xylosides, which bypass the requirement for core protein, did not bring oligosaccharide sulfation in mitotics to interphase levels. These observations indicate an inhibition of Golgi processing and are consistent with a generalized defect of membrane vesicle-mediated transport during mitosis.In their pioneering work on glycosaminoglycan (GAG) ~ synthesis by cultured cells, Kraemer and Tobey (14) showed that a significant fraction of trypsin-releasable (i.e., surface) GAGs was shed during mitosis. Although the Chinese hamster ovary (CHO) cells analyzed were grown in suspension, viewed from the perspective of recent studies of cell adhesion (e.g., reference 32), it seemed likely that the shedding of GAGs was related to the familiar ease with which mitotic cells are detached from monolayers. We hypothesized that any effect of shedding would be reinforced by a coordinate reduction in GAG synthesis that would delay replacement of surface GAGs, and that a rapid resumption of GAG synthesis in early G i would be required for cell reattachment.A parallel motivation for our studies arose from the accumulating evidence that membrane vesicle-mediated transport is depressed during mitosis. This is shown clearly in work from our laboratory demonstrating depression of endocytosis ( 1, 2) and transferrin recycling (35) and from that of Warren and colleagues showing a decrease in surface transferrin receptors (41), and in depression of histamine secretion (9). These studies focus primarily on fusion and budding events at the plasma membrane. In addition, the insertion of the G t Abbreviations used in this paper. CHO, Chinese hamster ovary; GAG, glycosaminoglycan.protein of vesicular stomatitis virus is also depressed during mitosis (42), which suggests a defect in its processing through the Golgi apparatus. Since carbohydrate chains of GAGs are largely assembled within the Golgi apparatus by multiple enzymes (31), a general defect in processing should affect GAG synthesis. Moreover, the apparent localization of sulfation to the trans-Gol~ apparatus (7, 44) would serve to focus on later steps of the processing sequence.We describe here the rates of labeled sulfate incorporation into CHO cells during mitosis, in their subsequent movement into G1, and in late G2. We followed incorporat...

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Section: Discussionmentioning

confidence: 92%

Glycosaminoglycan synthesis is depressed during mitosis and elevated during early G1.

Preston¹,

Regula²,

Sager³

et al. 1985

The Journal of Cell Biology

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“…FGF10-FGFR2b signaling activates the MAPK cascade, regulating epithelial FGFR gene expression as well as the expression of ECM proteins in the basement membrane (Rebustini et al, 2007). HS is critical for SMG branching morphogenesis, as the addition of b-D-xyloside, bacterial heparitinase or exogenous heparin, inhibits ex vivo SMG branching (Mori, 1994;Nakanishi, 1993;Thompson and Spooner, 1982;Thompson and Spooner, 1983). Importantly, HS biosynthesis and accumulation in the basement membrane is coordinated with epithelial cell proliferation and end bud expansion.…”

Section: Introductionmentioning

confidence: 99%

Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis

et al. 2007

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Heparan sulfate proteoglycans are essential for biological processes regulated by fibroblast growth factors (FGFs). Heparan sulfate (HS) regulates the activity of FGFs by acting as a coreceptor at the cell surface, enhancing FGF-FGFR affinity, and being a storage reservoir for FGFs in the extracellular matrix (ECM). Here we demonstrate a critical role for heparanase during mouse submandibular gland (SMG) branching morphogenesis. Heparanase, an endoglycosidase, colocalized with perlecan in the basement membrane and in epithelial clefts of SMGs. Inhibition of heparanase activity in organ culture decreased branching morphogenesis, and this inhibition was rescued specifically by FGF10 and not by other FGFs. By contrast, exogenous heparanase increased SMG branching and MAPK signaling and, surprisingly, when isolated epithelia were cultured in a three-dimensional ECM with FGF10, it increased the number of lateral branches and end buds. In a solid-phase binding assay, an FGF10-FGFR2b complex was released from the ECM by heparanase. In addition, surface plasmon resonance (SPR) analysis showed that FGF10 and the FGF10-FGFR2b complex bound to purified perlecan HS and could be released by heparanase. We used the FGF10-FGFR2b complex as a probe for HS in SMGs, and it colocalized with perlecan in the basement membrane and partly colocalized with syndecan 1 in the epithelium, and binding was reduced by treatment with heparanase. In summary, our results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK signaling, epithelial clefting, and lateral branch formation, which results in increased branching morphogenesis.

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“…In fact, it is known that synthesis disruption or enzyme degradation of a cer-tain number of these molecules such as collagen, certain proteoglycans and glycoproteins may interfere with epithelial folding, as occurs in branching of the salivary glands, lung and kidney primordia (Klein et al 1989;Nakanishi et al 1986;Spooner and Faubion 1980;Spooner et al 1985;Thompson and Spooner 1983), as well as in the invagination of the otic primordium (Gerchman et al 1991). It has been demonstrated that treatment with tunicamycin, a drug which inhibits N-linked glycosylation, diminishing the synthesis of glycosaminoglycans, disrupts otic primordium invagination (Yang and Hilfer 1982;Rausch and Hilfer 1988).…”

Section: Introductionmentioning

confidence: 99%

Basal lamina heparan sulphate proteoglycan is involved in otic placode invagination in chick embryos

Moro-Balbás

Gato

Alonso

et al. 2000

Anatomy and Embryology

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Formation of the otocyst from the otic placode appears to differ from invagination of other cup-shaped organ primordia. It is known that the cellular cytoskeleton plays a limited role in otic placode invagination, whilst the extracellular matrix underlying the otic primordium intervenes in the folding process. In this study we have analysed the role of the basal lamina heparan sulphate proteoglycan in otic primordium invagination. At 10 H.H. stage, heparan sulphate proteoglycan immunomarking begins to appear on the otic placode basal lamina, increasing noticeably at 13 H.H. stage, coinciding with maximum folding of the otic epithelium, and is still present at later stages. Enzyme degradation of heparan sulphate proteoglycan in the otic primordium basal lamina, by means of microinjection with heparinase III prior to folding, significantly disrupts invagination of the otic placode, which remains practically flat, with a significant reduction in the depth of the otic pit and an increase in the diameter of the otic opening. The immunocytochemistry analysis revealed a notable depletion of basal lamina heparan sulphate proteoglycan in the otic primordia microinjected with heparinase, with no statistically significant differences observed in the volume or rate of cell proliferation in the otic epithelium relative to the control, which suggests that heparan sulphate proteoglycan disruption does not interfere with the epithelial growth. In addition, a study of apoptosis distribution by the TUNEL method confirmed that treatment with heparinase does not cause interference with cell survival in the otic epithelium. Our findings support the theory that otic primordium invagination may be regulated, at least in part, by the basal lamina components, which might contribute towards anchoring the otic epithelium to adjacent structures.

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Proteoglycan and glycosaminoglycan synthesis in embryonic mouse salivary glands: effects of beta-D-xyloside, an inhibitor of branching morphogenesis.

Cited by 100 publications

References 35 publications

Glycosaminoglycan synthesis is depressed during mitosis and elevated during early G1.

Glycosaminoglycan synthesis is depressed during mitosis and elevated during early G1.

Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis

Basal lamina heparan sulphate proteoglycan is involved in otic placode invagination in chick embryos

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