The Experts below are selected from a list of 2895 Experts worldwide ranked by ideXlab platform
Kimio Akagawa - One of the best experts on this subject based on the ideXlab platform.
-
The Syntaxin 5 Isoforms Syx5 and Syx5L have Distinct Effects on the Processing of β-amyloid Precursor Protein
The Journal of Biochemistry, 2009Co-Authors: Kei Suga, Ayako Saito, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:In this study, we examined the interaction of Syntaxin 5L (Syx5L), a Syx5 isoform that has an N-terminal extension containing a di-arginine ER-retrieval motif, with presenilin (PS) and its effects on the processing of β-amyloid precursor protein (βAPP). Similar to Syx5, Syx5L bound to PS1 Holoprotein but not to its N- or C-terminal fragments. Unlike Syx5, Syx5L overexpression did not cause marked accumulation of intracellular βAPP Holoprotein, and did not inhibit amyloid β peptide (Aβ) secretion. Analyses using deletion mutants of Syx5L revealed that, in addition to the difference in the intracellular localization between the isoforms, the presence of the N-terminal extension in Syx5L was critical for suppressing its inhibition of βAPP processing. Treatment of cells that overexpressed Syx5L with brefeldin A, an inhibitor of transport from the ER to the Golgi compartments, resulted in substantial accumulation of intracellular βAPP Holoprotein and reduction in the secretion of Aβ. Although Syx5 and Syx5L share lengthy regions of amino acid identity, they appear to play distinct roles in modulating the metabolism and trafficking of βAPP in the early secretory compartment.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects beta-amyloid peptide production.
The Biochemical journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects β-amyloid peptide production
Biochemical Journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
Kei Suga - One of the best experts on this subject based on the ideXlab platform.
-
The Syntaxin 5 Isoforms Syx5 and Syx5L have Distinct Effects on the Processing of β-amyloid Precursor Protein
The Journal of Biochemistry, 2009Co-Authors: Kei Suga, Ayako Saito, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:In this study, we examined the interaction of Syntaxin 5L (Syx5L), a Syx5 isoform that has an N-terminal extension containing a di-arginine ER-retrieval motif, with presenilin (PS) and its effects on the processing of β-amyloid precursor protein (βAPP). Similar to Syx5, Syx5L bound to PS1 Holoprotein but not to its N- or C-terminal fragments. Unlike Syx5, Syx5L overexpression did not cause marked accumulation of intracellular βAPP Holoprotein, and did not inhibit amyloid β peptide (Aβ) secretion. Analyses using deletion mutants of Syx5L revealed that, in addition to the difference in the intracellular localization between the isoforms, the presence of the N-terminal extension in Syx5L was critical for suppressing its inhibition of βAPP processing. Treatment of cells that overexpressed Syx5L with brefeldin A, an inhibitor of transport from the ER to the Golgi compartments, resulted in substantial accumulation of intracellular βAPP Holoprotein and reduction in the secretion of Aβ. Although Syx5 and Syx5L share lengthy regions of amino acid identity, they appear to play distinct roles in modulating the metabolism and trafficking of βAPP in the early secretory compartment.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects beta-amyloid peptide production.
The Biochemical journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects β-amyloid peptide production
Biochemical Journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
Takami Tomiyama - One of the best experts on this subject based on the ideXlab platform.
-
The Syntaxin 5 Isoforms Syx5 and Syx5L have Distinct Effects on the Processing of β-amyloid Precursor Protein
The Journal of Biochemistry, 2009Co-Authors: Kei Suga, Ayako Saito, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:In this study, we examined the interaction of Syntaxin 5L (Syx5L), a Syx5 isoform that has an N-terminal extension containing a di-arginine ER-retrieval motif, with presenilin (PS) and its effects on the processing of β-amyloid precursor protein (βAPP). Similar to Syx5, Syx5L bound to PS1 Holoprotein but not to its N- or C-terminal fragments. Unlike Syx5, Syx5L overexpression did not cause marked accumulation of intracellular βAPP Holoprotein, and did not inhibit amyloid β peptide (Aβ) secretion. Analyses using deletion mutants of Syx5L revealed that, in addition to the difference in the intracellular localization between the isoforms, the presence of the N-terminal extension in Syx5L was critical for suppressing its inhibition of βAPP processing. Treatment of cells that overexpressed Syx5L with brefeldin A, an inhibitor of transport from the ER to the Golgi compartments, resulted in substantial accumulation of intracellular βAPP Holoprotein and reduction in the secretion of Aβ. Although Syx5 and Syx5L share lengthy regions of amino acid identity, they appear to play distinct roles in modulating the metabolism and trafficking of βAPP in the early secretory compartment.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects beta-amyloid peptide production.
The Biochemical journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects β-amyloid peptide production
Biochemical Journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
Hiroshi Mori - One of the best experts on this subject based on the ideXlab platform.
-
The Syntaxin 5 Isoforms Syx5 and Syx5L have Distinct Effects on the Processing of β-amyloid Precursor Protein
The Journal of Biochemistry, 2009Co-Authors: Kei Suga, Ayako Saito, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:In this study, we examined the interaction of Syntaxin 5L (Syx5L), a Syx5 isoform that has an N-terminal extension containing a di-arginine ER-retrieval motif, with presenilin (PS) and its effects on the processing of β-amyloid precursor protein (βAPP). Similar to Syx5, Syx5L bound to PS1 Holoprotein but not to its N- or C-terminal fragments. Unlike Syx5, Syx5L overexpression did not cause marked accumulation of intracellular βAPP Holoprotein, and did not inhibit amyloid β peptide (Aβ) secretion. Analyses using deletion mutants of Syx5L revealed that, in addition to the difference in the intracellular localization between the isoforms, the presence of the N-terminal extension in Syx5L was critical for suppressing its inhibition of βAPP processing. Treatment of cells that overexpressed Syx5L with brefeldin A, an inhibitor of transport from the ER to the Golgi compartments, resulted in substantial accumulation of intracellular βAPP Holoprotein and reduction in the secretion of Aβ. Although Syx5 and Syx5L share lengthy regions of amino acid identity, they appear to play distinct roles in modulating the metabolism and trafficking of βAPP in the early secretory compartment.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects beta-amyloid peptide production.
The Biochemical journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
-
Syntaxin 5 interacts with presenilin Holoproteins, but not with their N- or C-terminal fragments, and affects β-amyloid peptide production
Biochemical Journal, 2004Co-Authors: Kei Suga, Takami Tomiyama, Hiroshi Mori, Kimio AkagawaAbstract:Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)-Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS Holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS Holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS Holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1DeltaE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS Holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS Holoproteins and the beta-amyloid precursor protein, and reduced the secretion of the Abeta (amyloid beta) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of beta-amyloid precursor protein in the early secretory compartments.
Dora M. Kovacs - One of the best experts on this subject based on the ideXlab platform.
-
Novel N-terminal Cleavage of APP Precludes Aβ Generation in ACAT-Defective AC29 Cells
Journal of Molecular Neuroscience, 2008Co-Authors: Henri J. Huttunen, Luigi Puglielli, Blake C. Ellis, Laura A. Mackenzie Ingano, Dora M. KovacsAbstract:A common pathogenic event that occurs in all forms of Alzheimer’s disease is the progressive accumulation of amyloid β-peptide (Aβ) in brain regions responsible for higher cognitive functions. Inhibition of acyl-coenzyme A: cholesterol acyltransferase (ACAT), which generates intracellular cholesteryl esters from free cholesterol and fatty acids, reduces the biogenesis of the Aβ from the amyloid precursor protein (APP). Here we have used AC29 cells, defective in ACAT activity, to show that ACAT activity steers APP either toward or away from a novel proteolytic pathway that replaces both α and the amyloidogenic β cleavages of APP. This alternative pathway involves a novel cleavage of APP Holoprotein at Glu281, which correlates with reduced ACAT activity and Aβ generation in AC29 cells. This sterol-dependent cleavage of APP occurs in the endosomal compartment after internalization of cell surface APP. The resulting novel C-terminal fragment APP-C470 is destined to proteasomal degradation limiting the availability of APP for the Aβ generating system. The proportion of APP molecules that are directed to the novel cleavage pathway is regulated by the ratio of free cholesterol and cholesteryl esters in cells. These results suggest that subcellular cholesterol distribution may be an important regulator of the cellular fate of APP Holoprotein and that there may exist several competing proteolytic systems responsible for APP processing within the endosomal compartment.