Glomerular basement membrane proteoglycans are derived from a large precursor.

Klein, David J.; Brown, David M.; Oegema, Theodore R.; Brenchley, Paul; Anderson, John C.; Dickinson, Mark A. J.; Horigan, Elizabeth A.; Hassell, John R.

doi:10.1083/jcb.106.3.963

Cited by 98 publications

(35 citation statements)

References 53 publications

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“…Previous studies using the Engelbreth-HolmSwarm (EHS) tumor have described perlecan with different sizes of core proteins and both HS and CS/DS GAG chains. [35][36][37][38] GAG-attachment sites on perlecan are grouped at the N-terminus in domain I of the perlecan core protein, and although HS are the primary GAG attached at these sites, they can be substituted with CS or DS GAG chains. 39 Recently, domains IV and V of this 5-domain core protein were shown to be capable of bearing GAG chains 40 and may provide greater potential for diversity in GAG attachment.…”

Section: Discussionmentioning

confidence: 99%

High Glucose–Induced Alterations in Subendothelial Matrix Perlecan Leads to Increased Monocyte Binding

Vogl-Willis

Edwards

2004

ATVB

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Objective-Hyperglycemia is an independent risk factor for cardiovascular disease in diabetic patients, although the link between the two is unknown. These studies were designed to model effects of high glucose on an early event in atherogenesis: the binding of monocytes to subendothelial matrix (SEM). Methods and Results-SEM was prepared from human bovine aortic endothelial cells (HAECs) and bovine aortic endothelial cells (BAECs) cultured in the presence of low (5

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Section: Discussionmentioning

confidence: 99%

High Glucose–Induced Alterations in Subendothelial Matrix Perlecan Leads to Increased Monocyte Binding

Vogl-Willis

Edwards

2004

ATVB

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“…The medium was lyophilized and reconstituted in 50 l of DW. 10-l aliquots, with and without digestion by chondroitinase ABC and heparatinase combined, were subjected to SDS-polyacrylamide gel electrophoresis in 7.5% acrylamide gels and transferred to nitrocellulose for Western blot analysis using rabbit antiserum against perlecan (24). Western blots were done from two separate transfections for each construct.…”

Section: Methodsmentioning

confidence: 99%

Identification of Sites in Domain I of Perlecan That Regulate Heparan Sulfate Synthesis

Dolan

Horchar

Rigatti

et al. 1997

Journal of Biological Chemistry

106

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Perlecan is primarily a heparan sulfate containing proteoglycan found in all basement membranes. Rotary shadowed images of perlecan show it to contain three glycosaminoglycan (GAG) side chains extending from one end of its core protein. Domain I is at the N terminus of perlecan and contains three closely spaced Ser-GlyAsp sequences that may serve in GAG attachment. We evaluated the serines in these three sequences for GAG attachment by preparing a cDNA construct encoding for the N-terminal half (domains I, II, and III) of perlecan and then a series of constructs containing deletions and mutations within domain I of the domain I/II/III construct, expressing these constructs in COS-7 cells, and then analyzing the recombinant product for GAG side chains and GAG type. The results showed that all three serine residues in the Ser-Gly-Asp sequences in domain I can accept both chondroitin and heparan sulfate side chains but that a cluster of acidic residues N-terminal to these sequences is the primary determinant responsible for targeting these sites for heparan sulfate. Furthermore, there are two elements that can enhance heparan sulfate synthesis at a targeted site: 1) the presence of a the SEA module in the C-terminal region of domain I and 2) the presence of multiple acceptors in close proximity. These results indicate that the proportion of heparan and chondroitin sulfate at any one site in domain I of perlecan is regulated by multiple factors.

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“…Biosynthetic and immunological studies demonstrated that they comprise various fragments of the molecule identified in the EHS tumor [142]. Whether these fragments are specific processing products or artifacts of isolation remains uncertain.…”

Section: Low-density Heparan Sulfate Proteoglycanmentioning

confidence: 99%

Structure and biological activity of basement membrane proteins

Timpl

1989

European Journal of Biochemistry

926

394

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Collagen type IV, laminin, heparan sulfate proteoglycans, nidogen (entactin) and SPARC) represent major structural proteins of basement membranes. They are well-characterized in their domain structures, amino acid sequences and potentials for molecular interactions. Such interactions include self-assembly processes and heterotypic binding between individual constituents, as well as binding of calcium (laminin, and are likely to be used for basement membrane assembly. Laminin, collagen IV and nidogen also possess several cell-binding sites which interact with distinct cellular receptors. Some evidence exists that those interactions are involved in the control of cell behaviour. These observations have provided a more defined understanding of basement membrane function and the definition of new research goals in the future.All multicellular animals possess various extracellular matrices. They determine body shape and stability, compartmentalization of organs and several cellular activities. These matrices include ubiquitously occurring basement membranes which are 20 -200-nm-broad deposits of some specific proteins in close proximity to epithelial, muscle, fat and nerve cells. Basement membranes are found in vertebrates and invertebrates except sponges and are produced as the first matrix during embryonic development. They are considered to control cell phenotype, tissue invasion of cells and filtration of macromolecules through glomeruli [I -41. This implies a defined supramolecular architecture for basement membranes and a distinct repertoire of biological activities expressed as the sum of their individual constituents. Yet, electron microscopy has so far revealed few details of basement membrane structure which, after staining, presents as two amorphous zones (the lamina lucida and the lamina densa) distinguished by different electron densities [5].Basement membranes are normally but not exclusively produced and deposited by cells which then remain in close contact with these structures. These contacts are mediated by specific cellular receptors which bind to some defined extracellular ligands [l -31. Other noncovalent molecular interactions maintain the matrix structure and covalent cross-links make basement membranes rather insoluble even in denaturing solvents. The increasing use of tumor models, such as the Engelbreth-Holm-Swarm (EHS) mouse tumor [6], which produce large amounts of soluble basement-membrane material has over the past decade allowed a comprehensive characterization of the major components. The progress in our understanding of the structure, biology and pathology of basement membranes 11-5 , 7 -101 as well as some methodological aspects [lo, 111 have been recently reviewed. The preCorrespondence to R . Timpl.

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Glomerular basement membrane proteoglycans are derived from a large precursor.

Cited by 98 publications

References 53 publications

High Glucose–Induced Alterations in Subendothelial Matrix Perlecan Leads to Increased Monocyte Binding

High Glucose–Induced Alterations in Subendothelial Matrix Perlecan Leads to Increased Monocyte Binding

Identification of Sites in Domain I of Perlecan That Regulate Heparan Sulfate Synthesis

Structure and biological activity of basement membrane proteins

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