The Experts below are selected from a list of 143514 Experts worldwide ranked by ideXlab platform
Harold P Erickson - One of the best experts on this subject based on the ideXlab platform.
-
mitogenesis Cell migration and loss of focal adhesions induced by tenascin c interacting with its Cell Surface Receptor annexin ii
Molecular Biology of the Cell, 1996Co-Authors: Chang Y Chung, Joanne E Murphyullrich, Harold P EricksonAbstract:Abstract In a previous study we demonstrated that the alternatively spliced region of tenascin-C, TNfnA-D, bound with high affinity to a Cell Surface Receptor, annexin II. In the present study we demonstrate three changes in Cellular activity that are produced by adding intact tenascin-C or TNfnA-D to Cells, and we show that all three activities are blocked by antibodies against annexin II. 1) TNfnA-D added to confluent endothelial Cells induced loss of focal adhesions. 2) TNfnA-D produced a mitogenic response of confluent, growth-arrested endothelial Cells in 1% serum. TNfnA-D stimulated mitogenesis only when it was added to Cells before or during exposure to other mitogens, such as basic fibroblast growth factor or serum. Thus the effect of TNfnA-D seems to be to facilitate the subsequent response to growth factors. 3) TNfnA-D enhanced Cell migration in a Cell culture wound assay. Antibodies to annexin II blocked all three Cellular responses to TNfnA-D. These data show that annexin II Receptors on endothelial Cells mediate several Cell regulatory functions attributed to tenascin-C, potentially through modulation of intraCellular signalling pathways.
-
mitogenesis Cell migration and loss of focal adhesions induced by tenascin c interacting with its Cell Surface Receptor annexin ii
Molecular Biology of the Cell, 1996Co-Authors: Chang Y Chung, Joanne E Murphyullrich, Harold P EricksonAbstract:In a previous study we demonstrated that the alternatively spliced region of tenascin-C, TNfnA-D, bound with high affinity to a Cell Surface Receptor, annexin II. In the present study we demonstrat...
Motoyoshi Nomizu - One of the best experts on this subject based on the ideXlab platform.
-
Cell Surface Receptor specific scaffold requirements for adhesion to laminin derived peptide chitosan membranes
Biomaterials, 2010Co-Authors: Kentaro Hozumi, Dai Otagiri, Chikara Fujimori, Yamato Kikkawa, Yuji Yamada, Ayano Sasaki, Yuki Wakai, Tatsuya Uchida, Fumihiko Katagiri, Motoyoshi NomizuAbstract:Abstract Scaffolds are used for bioengineering to regulate Cellular functions. Previously, we developed laminin-derived peptide–conjugated chitosan membranes for Cell engineering. Here, we determined whether changes in the chitosan scaffold altered the Cellular response. When an αvβ3 integrin-binding peptide A99a (ALRGDN) was conjugated on chitosan membranes of varying density (1.5–1500 ng/mm 2 ), Cell adhesion was altered depending on the amount of chitosan. 3 or 30 ng/mm 2 of the A99a-chitosan membrane effectively promoted Cell attachment, Cell spreading with well-organized actin stress fibers, phosphorylation of FAK Tyr397, and neurite outgrowth. In contrast, syndecan-binding peptide AG73 (RKRLQVQLSIRT) conjugated chitosan membranes density (1.5–1500 ng/mm 2 ) promoted similar biological activities at all of the concentrations tested. These results suggest that integrin-mediated Cell adhesion is sensitive to the scaffold condition. To improve the function of integrin-mediated biological activities on a large amount of scaffold, we designed an A99a/AG73 mixed peptide–chitosan membrane. The mixed peptide–chitosan membrane promoted the strongest biological activities at 150–1500 ng/mm 2 of chitosan membrane. We conclude that the A99a/AG73 mixed peptide–chitosan membrane effectively interacts with both integrins and syndecans and is a useful multi-functional biomaterial.
-
Cell Surface Receptor-specific scaffold requirements for adhesion to laminin-derived peptide–chitosan membranes
Biomaterials, 2010Co-Authors: Kentaro Hozumi, Dai Otagiri, Chikara Fujimori, Yamato Kikkawa, Yuji Yamada, Ayano Sasaki, Yuki Wakai, Tatsuya Uchida, Fumihiko Katagiri, Motoyoshi NomizuAbstract:Abstract Scaffolds are used for bioengineering to regulate Cellular functions. Previously, we developed laminin-derived peptide–conjugated chitosan membranes for Cell engineering. Here, we determined whether changes in the chitosan scaffold altered the Cellular response. When an αvβ3 integrin-binding peptide A99a (ALRGDN) was conjugated on chitosan membranes of varying density (1.5–1500 ng/mm 2 ), Cell adhesion was altered depending on the amount of chitosan. 3 or 30 ng/mm 2 of the A99a-chitosan membrane effectively promoted Cell attachment, Cell spreading with well-organized actin stress fibers, phosphorylation of FAK Tyr397, and neurite outgrowth. In contrast, syndecan-binding peptide AG73 (RKRLQVQLSIRT) conjugated chitosan membranes density (1.5–1500 ng/mm 2 ) promoted similar biological activities at all of the concentrations tested. These results suggest that integrin-mediated Cell adhesion is sensitive to the scaffold condition. To improve the function of integrin-mediated biological activities on a large amount of scaffold, we designed an A99a/AG73 mixed peptide–chitosan membrane. The mixed peptide–chitosan membrane promoted the strongest biological activities at 150–1500 ng/mm 2 of chitosan membrane. We conclude that the A99a/AG73 mixed peptide–chitosan membrane effectively interacts with both integrins and syndecans and is a useful multi-functional biomaterial.
Chang Y Chung - One of the best experts on this subject based on the ideXlab platform.
-
mitogenesis Cell migration and loss of focal adhesions induced by tenascin c interacting with its Cell Surface Receptor annexin ii
Molecular Biology of the Cell, 1996Co-Authors: Chang Y Chung, Joanne E Murphyullrich, Harold P EricksonAbstract:Abstract In a previous study we demonstrated that the alternatively spliced region of tenascin-C, TNfnA-D, bound with high affinity to a Cell Surface Receptor, annexin II. In the present study we demonstrate three changes in Cellular activity that are produced by adding intact tenascin-C or TNfnA-D to Cells, and we show that all three activities are blocked by antibodies against annexin II. 1) TNfnA-D added to confluent endothelial Cells induced loss of focal adhesions. 2) TNfnA-D produced a mitogenic response of confluent, growth-arrested endothelial Cells in 1% serum. TNfnA-D stimulated mitogenesis only when it was added to Cells before or during exposure to other mitogens, such as basic fibroblast growth factor or serum. Thus the effect of TNfnA-D seems to be to facilitate the subsequent response to growth factors. 3) TNfnA-D enhanced Cell migration in a Cell culture wound assay. Antibodies to annexin II blocked all three Cellular responses to TNfnA-D. These data show that annexin II Receptors on endothelial Cells mediate several Cell regulatory functions attributed to tenascin-C, potentially through modulation of intraCellular signalling pathways.
-
mitogenesis Cell migration and loss of focal adhesions induced by tenascin c interacting with its Cell Surface Receptor annexin ii
Molecular Biology of the Cell, 1996Co-Authors: Chang Y Chung, Joanne E Murphyullrich, Harold P EricksonAbstract:In a previous study we demonstrated that the alternatively spliced region of tenascin-C, TNfnA-D, bound with high affinity to a Cell Surface Receptor, annexin II. In the present study we demonstrat...
William S Hlavacek - One of the best experts on this subject based on the ideXlab platform.
-
modeling multivalent ligand Receptor interactions with steric constraints on configurations of Cell Surface Receptor aggregates
Biophysical Journal, 2010Co-Authors: Michael I Monine, Richard G Posner, Paul B Savage, James R Faeder, William S HlavacekAbstract:We use flow cytometry to characterize equilibrium binding of a fluorophore-labeled trivalent model antigen to bivalent IgE-FceRI complexes on RBL Cells. We find that flow cytometric measurements are consistent with an equilibrium model for ligand-Receptor binding in which binding sites are assumed to be equivalent and ligand-induced Receptor aggregates are assumed to be acyclic. However, this model predicts extensive Receptor aggregation at antigen concentrations that yield strong Cellular secretory responses, which is inconsistent with the expectation that large Receptor aggregates should inhibit such responses. To investigate possible explanations for this discrepancy, we evaluate four rule-based models for interaction of a trivalent ligand with a bivalent Cell-Surface Receptor that relax simplifying assumptions of the equilibrium model. These models are simulated using a rule-based kinetic Monte Carlo approach to investigate the kinetics of ligand-induced Receptor aggregation and to study how the kinetics and equilibria of ligand-Receptor interaction are affected by steric constraints on Receptor aggregate configurations and by the formation of cyclic Receptor aggregates. The results suggest that formation of linear chains of cyclic Receptor dimers may be important for generating secretory signals. Steric effects that limit Receptor aggregation and transient formation of small Receptor aggregates may also be important.
-
modeling multivalent ligand Receptor interactions with steric constraints on configurations of Cell Surface Receptor aggregates
PLOS Computational Biology, 2008Co-Authors: Michael I Monine, Richard G Posner, Paul B Savage, James R Faeder, William S HlavacekAbstract:Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent Cell-Surface Receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of Receptor aggregates, and finally, a model that accounts for cyclic Receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small more » and large aggregate formation and the percolation phase transition that occurs in this system. « less
Raymond C Stevens - One of the best experts on this subject based on the ideXlab platform.
-
structural basis of Cell Surface Receptor recognition by botulinum neurotoxin b
Nature, 2006Co-Authors: Qing Chai, Joseph W Arndt, Min Dong, William H Tepp, Eric A Johnson, Edwin R Chapman, Raymond C StevensAbstract:Botulinum neurotoxins (BoNTs) are potent bacterial toxins that cause paralysis at femtomolar concentrations by blocking neurotransmitter release. A 'double Receptor' model has been proposed in which BoNTs recognize nerve terminals via interactions with both gangliosides and protein Receptors that mediate their entry. Of seven BoNTs (subtypes A-G), the putative Receptors for BoNT/A, BoNT/B and BoNT/G have been identified, but the molecular details that govern recognition remain undefined. Here we report the crystal structure of full-length BoNT/B in complex with the synaptotagmin II (Syt-II) recognition domain at 2.6 A resolution. The structure of the complex reveals that Syt-II forms a short helix that binds to a hydrophobic groove within the binding domain of BoNT/B. In addition, mutagenesis of amino acid residues within this interface on Syt-II affects binding of BoNT/B. Structural and sequence analysis reveals that this hydrophobic groove is conserved in the BoNT/G and BoNT/B subtypes, but varies in other clostridial neurotoxins. Furthermore, molecular docking studies using the ganglioside G(T1b) indicate that its binding site is more extensive than previously proposed and might form contacts with both BoNT/B and synaptotagmin. The results provide structural insights into how BoNTs recognize protein Receptors and reveal a promising target for blocking toxin-Receptor recognition.
-
structural basis of Cell Surface Receptor recognition by botulinum neurotoxin b
Nature, 2006Co-Authors: Qing Chai, Joseph W Arndt, Min Dong, William H Tepp, Eric A Johnson, Edwin R Chapman, Raymond C StevensAbstract:Botulinum toxins, produced by Clostridia botulinum, are a potential biological hazard to humans and a potential bioweapons threat. The toxins are potent inhibitors of neurotransmitter release at synapses, and it is this property that causes the neuroparalytic syndrome known as botulism. Two related papers now report the crystal structure of botulinum toxin B bound to its Receptor on the exposed Surface of the neuron. This will provide insight into the high affinity and specificity of this interaction, and aid in the development of antibotulism vaccines and drugs. One of two papers that describe how botulinum toxins produced by Clostridium botulinum are potent inhibitors of neurotransmitter release by elucidating the crystal structure of botulinum toxin B bound to its Receptor. Botulinum neurotoxins (BoNTs) are potent bacterial toxins that cause paralysis at femtomolar concentrations1 by blocking neurotransmitter release. A ‘double Receptor’ model has been proposed in which BoNTs recognize nerve terminals via interactions with both gangliosides and protein Receptors that mediate their entry2. Of seven BoNTs (subtypes A–G), the putative Receptors for BoNT/A3,4, BoNT/B5,6 and BoNT/G7 have been identified, but the molecular details that govern recognition remain undefined. Here we report the crystal structure of full-length BoNT/B in complex with the synaptotagmin II (Syt-II) recognition domain at 2.6 A resolution. The structure of the complex reveals that Syt-II forms a short helix that binds to a hydrophobic groove within the binding domain of BoNT/B. In addition, mutagenesis of amino acid residues within this interface on Syt-II affects binding of BoNT/B. Structural and sequence analysis reveals that this hydrophobic groove is conserved in the BoNT/G and BoNT/B subtypes, but varies in other clostridial neurotoxins. Furthermore, molecular docking studies using the ganglioside GT1b indicate that its binding site is more extensive than previously proposed and might form contacts with both BoNT/B and synaptotagmin. The results provide structural insights into how BoNTs recognize protein Receptors and reveal a promising target for blocking toxin–Receptor recognition.