The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Lynn Y. Sakai - One of the best experts on this subject based on the ideXlab platform.
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versican interacts with fibrillin 1 and links extracellular microfibrils to other connective tissue networks
Journal of Biological Chemistry, 2002Co-Authors: Zenzo Isogai, D.r. Keene, Anders Aspberg, Dieter P Reinhardt, Lynn Y. SakaiAbstract:Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant Lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other Lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.
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versican interacts with fibrillin 1 and links extracellular microfibrils to other connective tissue networks
Journal of Biological Chemistry, 2002Co-Authors: Zenzo Isogai, D.r. Keene, Anders Aspberg, Dieter P Reinhardt, Lynn Y. SakaiAbstract:Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant Lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other Lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.
Anders Aspberg - One of the best experts on this subject based on the ideXlab platform.
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versican interacts with fibrillin 1 and links extracellular microfibrils to other connective tissue networks
Journal of Biological Chemistry, 2002Co-Authors: Zenzo Isogai, D.r. Keene, Anders Aspberg, Dieter P Reinhardt, Lynn Y. SakaiAbstract:Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant Lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other Lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.
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versican interacts with fibrillin 1 and links extracellular microfibrils to other connective tissue networks
Journal of Biological Chemistry, 2002Co-Authors: Zenzo Isogai, D.r. Keene, Anders Aspberg, Dieter P Reinhardt, Lynn Y. SakaiAbstract:Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant Lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other Lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.
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the c type lectin domains of Lecticans a family of aggregating chondroitin sulfate proteoglycans bind tenascin r by protein protein interactions independent of carbohydrate moiety
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Anders Aspberg, Ryu Miura, Melitta Schachner, Dick Heinegard, Sandrine Bourdoulous, Motoyuki Shimonaka, Erkki Ruoslahti, Yu YamaguchiAbstract:The Lecticans are a family of chondroitin sulfate proteoglycans including aggrecan, versican, neurocan, and brevican. The C-terminal globular domains of Lecticans are structurally related to selectins, consisting of a C-type lectin domain flanked by epidermal growth factor and complement regulatory protein domains. The C-type lectin domain of versican has been shown to bind tenascin-R, an extracellular matrix protein specifically expressed in the nervous system, and the interaction was presumed to be mediated by a carbohydrate–protein interaction. In this paper, we show that the C-type lectin domain of brevican, another Lectican that is specifically expressed in the nervous system, also binds tenascin-R. Surprisingly, this interaction is mediated by a protein–protein interaction through the fibronectin type III domains 3–5 of tenascin-R, independent of any carbohydrates or sulfated amino acids. The lectin domains of versican and other Lecticans also bind the same domain of tenascin-R by protein–protein interactions. Surface plasmon resonance analysis revealed that brevican lectin has at least a 10-fold higher affinity than the other Lectican lectins. Tenascin-R is coprecipitated with brevican from adult rat brain extracts, suggesting that tenascin-R and brevican form complexes in vivo. These results demonstrate that the C-type lectin domain can interact with fibronectin type III domains through protein–protein interactions, and suggest that brevican is a physiological tenascin-R ligand in the adult brain.
Zenzo Isogai - One of the best experts on this subject based on the ideXlab platform.
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versican interacts with fibrillin 1 and links extracellular microfibrils to other connective tissue networks
Journal of Biological Chemistry, 2002Co-Authors: Zenzo Isogai, D.r. Keene, Anders Aspberg, Dieter P Reinhardt, Lynn Y. SakaiAbstract:Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant Lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other Lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.
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versican interacts with fibrillin 1 and links extracellular microfibrils to other connective tissue networks
Journal of Biological Chemistry, 2002Co-Authors: Zenzo Isogai, D.r. Keene, Anders Aspberg, Dieter P Reinhardt, Lynn Y. SakaiAbstract:Fibrillin-containing microfibrils are polymeric structures that are difficult to extract from connective tissues. Proteolytic digestion of tissues has been utilized to release microfibrils for study. Few of the molecules that connect microfibrils to other elements in the matrix have been identified. In this study, electron microscopic immunolocalization of anti-versican antibodies in tissues and in extracted microfibrils demonstrated that the C-terminal region of versican is found associated with fibrillin microfibrils. Extraction of microfibrils followed by treatment of microfibrils under dissociating conditions suggested that the versican C terminus is covalently bound to microfibrils. Binding assays using recombinant fibrillin-1 polypeptides and recombinant Lectican lectin domains indicated that the versican lectin domain binds to specific fibrillin-1 polypeptides. The versican lectin domain also bound to molecules comigrating with authentic fibrillin-1 monomers in anassay using cell culture medium. In assays using microfibrils, the versican lectin domain demonstrated preferential binding compared with other Lecticans. Binding was calcium-dependent. The binding site for versican in microfibrils is most likely within a region of fibrillin-1 between calcium-binding epidermal growth factor-like domains 11 and 21. Human mutations irk this region can result in severe forms of the Marfan syndrome ("neonatal" Marfan syndrome). The connection between versican and fibrillin microfibrils may be functionally significant, particularly in cardiovascular tissues.
Burton B Yang - One of the best experts on this subject based on the ideXlab platform.
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Versican Mediates Mesenchymal-Epithelial Transition
Molecular biology of the cell, 2006Co-Authors: Wang Sheng, Guizhi Wang, David P. La Pierre, Jianping Wen, Zhaoqun Deng, Chung-kwun Amy Wong, Daniel Y. Lee, Burton B YangAbstract:Versican is a large extracellular chondroitin sulfate proteoglycan that belongs to the family of Lecticans. Alternative splicing of versican generates at least four isoforms named V0, V1, V2, and V3. We show here that ectopic expression of versican V1 isoform induced mesenchymal-epithelial transition (MET) in NIH3T3 fibroblasts, and inhibition of endogenous versican expression abolished the MET in metanephric mesenchyme. MET in NIH3T3 cells was demonstrated by morphological changes and dramatic alterations in both membrane and cytoskeleton architecture. Molecular analysis showed that V1 promoted a "switch" in cadherin expression from N- to E-cadherin, resulting in epithelial specific adhesion junctions. V1 expression reduced vimentin levels and induced expression of occludin, an epithelial-specific marker, resulting in polarization of V1-transfected cells. Furthermore, an MSP (methylation-specific PCR) assay showed that N-cadherin expression was suppressed through methylation of its DNA promoter. Exogenous expression of N-cadherin in V1-transfected cells reversed V1's effect on cell aggregation. Reduction of E-cadherin expression by Snail transfection and siRNA targeting E-cadherin abolished V1-induced morphological alteration. Transfection of an siRNA construct targeting versican also reversed the changed morphology induced by V1 expression. Silencing of endogenous versican prevented MET of metanephric mesenchyme. Taken together, our results demonstrate the involvement of versican in MET: expression of versican is sufficient to induce MET in NIH3T3 fibroblasts and reduction of versican expression decreased MET in metanephric mesenchyme.
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the roles of versican v1 and v2 isoforms in cell proliferation and apoptosis
Molecular Biology of the Cell, 2005Co-Authors: Wang Sheng, Guizhi Wang, Jianping Wen, Yelina Wang, Jiyong Liang, Peng Sheng Zheng, Vivian Lee, Joyce M Slingerland, Dan Dumont, Burton B YangAbstract:Versican is a large chondroitin sulfate proteoglycan belonging to the Lectican family. Alternative splicing of versican generates at least four isoforms named V0, V1, V2, and V3. We have shown that the versican V1 isoform not only enhanced cell proliferation, but also modulated cell cycle progression and protected the cells from apoptosis. Futhermore, the V1 isoform was able to not only activate proto-oncogene EGFR expression and modulate its downstream signaling pathway, but also induce p27 degradation and enhance CDK2 kinase activity. As well, the V1 isoform down-regulated the expression of the proapoptotic protein Bad. By contrast, the V2 isoform exhibited opposite biological activities by inhibiting cell proliferation and down-regulated the expression of EGFR and cyclin A. Furthermore, V2 did not contribute apoptotic resistance to the cells. In light of these results, we are reporting opposite functions for the two versican isoforms whose expression is differentially regulated. Our studies suggest that the roles of these two isoforms are associated with the subdomains CSbeta and CSalpha, respectively. These results were confirmed by silencing the expression of versican V1 with small interfering RNA (siRNA), which abolished V1-enhanced cell proliferation and V1-induced reduction of apoptosis.
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The Roles of Versican V1 and V2 Isoforms in Cell Proliferation and Apoptosis
2004Co-Authors: Peng Sheng Zheng, Vivian Lee, Dan Dumont, Joyce Slingerl, Burton B YangAbstract:Versican is a large chondroitin sulfate proteoglycan belonging to the Lectican family. Alternative splicing of versican generates at least four isoforms named V0, V1, V2, and V3. We have shown that the versican V1 isoform not only enhanced cell proliferation, but also modulated cell cycle progression and protected the cells from apoptosis. Futhermore, the V1 isoform was able to not only activate proto-oncogene EGFR expression and modulate its downstream signaling pathway, but also induce p27 degradation and enhance CDK2 kinase activity. As well, the V1 isoform down-regulated the expression of the proapoptotic protein Bad. By contrast, the V2 isoform exhibited opposite biological activities by inhibiting cell proliferation and down-regulated the expression of EGFR and cyclin A. Furthermore, V2 did not contribute apoptotic resistance to the cells. In light of these results, we are reporting opposite functions for the two versican isoforms whose expression is differentially regulated. Our studies suggest that the roles of these two isoforms are associated with the subdomains CS � and CS�, respectively. These results were confirmed by silencing the expression of versican V1 with small interfering RNA (siRNA), which abolished V1-enhanced cell proliferation and V1-induced reduction of apoptosis
Yu Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
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brevican is degraded by matrix metalloproteinases and aggrecanase 1 adamts4 at different sites
Journal of Biological Chemistry, 2000Co-Authors: Hiroyuki Nakamura, Kotaro Sugimoto, Isao Inoki, Kazuhiko Tanzawa, Hirokazu Matsuki, Ryu Miura, Yu Yamaguchi, Yutaka Fujii, Yasunori OkadaAbstract:Abstract Brevican is a member of the Lectican family of chondroitin sulfate proteoglycans that is predominantly expressed in the central nervous system. The susceptibility of brevican to digestion by matrix metalloproteinases (MMP-1, -2, -3, -7, -8, -9, -10, and -13 and membrane type 1 and 3 MMPs) and aggrecanase-1 (ADAMTS4) was examined. MMP-1, -2, -3, -7, -8, -10, and -13 degraded brevican into a few fragments with similar molecular masses, whereas the degradation products of aggrecanase-1 had apparently different sizes. NH2-terminal sequence analyses of the digestion fragments revealed that cleavages of the brevican core protein by these metalloproteinases occurred commonly within the central non-homologous domain. MMP-1, -2, -3, -7, -8, -10, and -13 preferentially attacked the Ala360–Phe361 bond, whereas aggrecanase-1 cleaved the Glu395–Ser396 bond, which are similar to the cleavage sites observed with cartilage proteoglycan (aggrecan) for the MMPs and aggrecanase-1, respectively. These data demonstrate that MMP-1, -2, -3, -7, -8, -10, and -13 and aggrecanase-1 digest brevican in a similar pattern to aggrecan and suggest that they may be responsible for the physiological turnover and pathological degradation of brevican.
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immunohistochemical evidence for the brevican tenascin r interaction colocalization in perineuronal nets suggests a physiological role for the interaction in the adult rat brain
The Journal of Comparative Neurology, 1999Co-Authors: Kazuki Hagihara, Ryu Miura, Rika Kosaki, Erik O Berglund, Barbara Ranscht, Yu YamaguchiAbstract:Brevican is one of the most abundant chondroitin sulfate proteoglycans in the adult rat brain. We have recently shown that the C-type lectin domain of brevican binds fibronectin type III domains 3–5 of tenascin-R. Here we report strong evidence for a physiological basis for this interaction. Substantial brevican immunoreactivity was detected in a number of nuclei and in the reticular formations throughout the midbrain and hindbrain, including, but not limited to, the deep cerebellar nuclei, the trapezoid body, the red nucleus, the oculomotor nucleus, the vestibular nucleus, the cochlear nucleus, the gigantocellular reticular nucleus, the motor trigeminal nucleus, and the lateral superior olive. Most of the brevican immunoreactivity exhibited pericellular and reticular staining patterns. In almost all of these sites, brevican immunoreactivity colocalized with that of tenascin-R, which was also substantially codistributed with versican, another member of the Lectican family. Detailed analysis revealed that the pericellular staining of brevican resembled that in perineuronal nets in which tenascin-R has been localized. Immunoelectron microscopy identified brevican immunoreactivity in the intercellular spaces surrounding presynaptic boutons and on their surfaces, but not in the synaptic clefts or in their immediate vicinity, a distribution pattern consistent with perineuronal nets. Taken together, our results provide strong evidence that the previously reported interactions between brevican and tenascin-R may play a functional role within the perineuronal nets. J. Comp. Neurol. 410:256–264, 1999. © 1999 Wiley-Liss, Inc.
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the c type lectin domains of Lecticans a family of aggregating chondroitin sulfate proteoglycans bind tenascin r by protein protein interactions independent of carbohydrate moiety
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Anders Aspberg, Ryu Miura, Melitta Schachner, Dick Heinegard, Sandrine Bourdoulous, Motoyuki Shimonaka, Erkki Ruoslahti, Yu YamaguchiAbstract:The Lecticans are a family of chondroitin sulfate proteoglycans including aggrecan, versican, neurocan, and brevican. The C-terminal globular domains of Lecticans are structurally related to selectins, consisting of a C-type lectin domain flanked by epidermal growth factor and complement regulatory protein domains. The C-type lectin domain of versican has been shown to bind tenascin-R, an extracellular matrix protein specifically expressed in the nervous system, and the interaction was presumed to be mediated by a carbohydrate–protein interaction. In this paper, we show that the C-type lectin domain of brevican, another Lectican that is specifically expressed in the nervous system, also binds tenascin-R. Surprisingly, this interaction is mediated by a protein–protein interaction through the fibronectin type III domains 3–5 of tenascin-R, independent of any carbohydrates or sulfated amino acids. The lectin domains of versican and other Lecticans also bind the same domain of tenascin-R by protein–protein interactions. Surface plasmon resonance analysis revealed that brevican lectin has at least a 10-fold higher affinity than the other Lectican lectins. Tenascin-R is coprecipitated with brevican from adult rat brain extracts, suggesting that tenascin-R and brevican form complexes in vivo. These results demonstrate that the C-type lectin domain can interact with fibronectin type III domains through protein–protein interactions, and suggest that brevican is a physiological tenascin-R ligand in the adult brain.