The Experts below are selected from a list of 15657 Experts worldwide ranked by ideXlab platform
Nicholas F. Larusso - One of the best experts on this subject based on the ideXlab platform.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
Debbie C Thurmond - One of the best experts on this subject based on the ideXlab platform.
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the Actin related p41arc subunit contributes to p21 activated kinase 1 pak1 mediated glucose uptake into skeletal muscle cells
Journal of Biological Chemistry, 2017Co-Authors: Ragadeepthi Tunduguru, Jeffrey S Elmendorf, Jing Zhang, Arianne Aslamy, Vishal A Salunkhe, Joseph T Brozinick, Debbie C ThurmondAbstract:Defects in translocation of the glucose transporter GLUT4 are associated with peripheral insulin resistance, preclinical diabetes, and progression to type 2 diabetes. GLUT4 recruitment to the plasma membrane of skeletal muscle cells requires F-Actin Remodeling. Insulin signaling in muscle requires p21-activated kinase-1 (PAK1), whose downstream signaling triggers Actin Remodeling, which promotes GLUT4 vesicle translocation and glucose uptake into skeletal muscle cells. Actin Remodeling is a cyclic process, and although PAK1 is known to initiate changes to the cortical Actin-binding protein cofilin to stimulate the depolymerizing arm of the cycle, how PAK1 might trigger the polymerizing arm of the cycle remains unresolved. Toward this, we investigated whether PAK1 contributes to the mechanisms involving the Actin-binding and -polymerizing proteins neural Wiskott-Aldrich syndrome protein (N-WASP), cortActin, and ARP2/3 subunits. We found that the Actin-polymerizing ARP2/3 subunit p41ARC is a PAK1 substrate in skeletal muscle cells. Moreover, co-immunoprecipitation experiments revealed that insulin stimulates p41ARC phosphorylation and increases its association with N-WASP coordinately with the associations of N-WASP with cortActin and Actin. Importantly, all of these associations were ablated by the PAK inhibitor IPA3, suggesting that PAK1 activation lies upstream of these Actin-polymerizing complexes. Using the N-WASP inhibitor wiskostatin, we further demonstrated that N-WASP is required for localized F-Actin polymerization, GLUT4 vesicle translocation, and glucose uptake. These results expand the model of insulin-stimulated glucose uptake in skeletal muscle cells by implicating p41ARC as a new component of the insulin-signaling cascade and connecting PAK1 signaling to N-WASP-cortActin-mediated Actin polymerization and GLUT4 vesicle translocation.
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signaling of the p21 activated kinase pak1 coordinates insulin stimulated Actin Remodeling and glucose uptake in skeletal muscle cells
Biochemical Pharmacology, 2014Co-Authors: Ragadeepthi Tunduguru, Tim T Chiu, Latha Ramalingam, Jeffrey S Elmendorf, Amira Klip, Debbie C ThurmondAbstract:Skeletal muscle accounts for ∼ 80% of postprandial glucose clearance, and skeletal muscle glucose clearance is crucial for maintaining insulin sensitivity and euglycemia. Insulin-stimulated glucose clearance/uptake entails recruitment of glucose transporter 4 (GLUT4) to the plasma membrane (PM) in a process that requires cortical F-Actin Remodeling; this process is dysregulated in Type 2 Diabetes. Recent studies have implicated PAK1 as a required element in GLUT4 recruitment in mouse skeletal muscle in vivo, although its underlying mechanism of action and requirement in glucose uptake remains undetermined. Toward this, we have employed the PAK1 inhibitor, IPA3, in studies using L6-GLUT4-myc muscle cells. IPA3 fully ablated insulin-stimulated GLUT4 translocation to the PM, corroborating the observation of ablated insulin-stimulated GLUT4 accumulation in the PM of skeletal muscle from PAK1(-/-) knockout mice. IPA3-treatment also abolished insulin-stimulated glucose uptake into skeletal myotubes. Mechanistically, live-cell imaging of myoblasts expressing the F-Actin biosensor LifeAct-GFP treated with IPA3 showed blunting of the normal insulin-induced cortical Actin Remodeling. This blunting was underpinned by a loss of normal insulin-stimulated cofilin dephosphorylation in IPA3-treated myoblasts. These findings expand upon the existing model of Actin Remodeling in glucose uptake, by placing insulin-stimulated PAK1 signaling as a required upstream step to facilitate Actin Remodeling and subsequent cofilin dephosphorylation. Active, dephosphorylated cofilin then provides the G-Actin substrate for continued F-Actin Remodeling to facilitate GLUT4 vesicle translocation for glucose uptake into the skeletal muscle cell.
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glucose regulates the cortical Actin network through modulation of cdc42 cycling to stimulate insulin secretion
American Journal of Physiology-cell Physiology, 2003Co-Authors: Angela K Nevins, Debbie C ThurmondAbstract:Glucose-stimulated insulin granule exocytosis in pancreatic β-cells involves cortical Actin Remodeling that results in the transient disruption of the interaction between polymerized Actin with the...
Xian Ming Chen - One of the best experts on this subject based on the ideXlab platform.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
Patrick L. Splinter - One of the best experts on this subject based on the ideXlab platform.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
Mark A. Mcniven - One of the best experts on this subject based on the ideXlab platform.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
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cdc42 and the Actin related protein neural wiskott aldrich syndrome protein network mediate cellular invasion by cryptosporidium parvum
Infection and Immunity, 2004Co-Authors: Xian Ming Chen, Daniel D Billadeau, James D Orth, Bing Q Huang, Patrick L. Splinter, Mark A. Mcniven, Nicholas F. LarussoAbstract:Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a Remodeling of the host cell Actin cytoskeleton. In addition, an Actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, Actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated Actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated Actin Remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell Actin Remodeling at the attachment site.
