The Experts below are selected from a list of 162 Experts worldwide ranked by ideXlab platform
Jesus Torresvazquez - One of the best experts on this subject based on the ideXlab platform.
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Aminoacyl Transfer RNA synthetase deficiency promotes angiogenesis via the unfolded protein response pathway
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Daniel Castranova, Andrew E Davis, Brigid D Lo, Mayumi F Miller, Paul J Paukstelis, Matthew R Swift, Van N Pham, Jesus TorresvazquezAbstract:Objective—Understanding the mechanisms regulating normal and pathological angiogenesis is of great scientific and clinical interest. In this report, we show that mutations in 2 different Aminoacyl-Transfer RNA synthetases, threonyl tRNA synthetase (tarsy58) or isoleucyl tRNA synthetase (iarsy68), lead to similar increased branching angiogenesis in developing zebrafish. Approach and Results—The unfolded protein response pathway is activated by Aminoacyl-Transfer RNA synthetase deficiencies, and we show that unfolded protein response genes atf4, atf6, and xbp1, as well as the key proangiogenic ligand vascular endothelial growth factor (vegfaa), are all upregulated in tarsy58 and iarsy68 mutants. Finally, we show that the protein kinase RNA-like endoplasmic reticulum kinase–activating transcription factor 4 arm of the unfolded protein response pathway is necessary for both the elevated vegfaa levels and increased angiogenesis observed in tarsy58 mutants. Conclusions—Our results suggest that endoplasmic retic...
Christopher S Francklyn - One of the best experts on this subject based on the ideXlab platform.
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Aminoacyl Transfer RNA synthetases connecting nutrient status to angiogenesis through the unfolded protein response
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Karen M Lounsbury, Christopher S FrancklynAbstract:Aminoacyl-Transfer RNA (tRNA) synthetases (AARSs) are well known for catalyzing the selective attachment of amino acids to their cognate tRNAs to ensure accurate protein translation. Evidence has accumulated in recent years that AARSs are involved in additional complex eukaryotic processes, including recruitment of immune cells and regulation of angiogenesis.1–4 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Castranova et al5 report an additional link between angiogenesis regulation and 2 specific AARSs, threonyl-tRNA synthetase (TARS) and isoleucyl-tRNA synthetase (IARS). In a genetic screen for altered vasculature, mutations in the tars and iars zebrafish genes were identified by classical genetic mapping and sequencing. The dysregulated vessel formation was associated with a premature stop codon in the tars gene and a point mutation in the iars gene. The phenotype caused by these mutations could be rescued by transgenes encoding the wild-type alleles. Further mechanistic studies showed that loss of TARS or IARS function leads to upregulation …
Paul J Paukstelis - One of the best experts on this subject based on the ideXlab platform.
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Aminoacyl Transfer RNA synthetase deficiency promotes angiogenesis via the unfolded protein response pathway
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Daniel Castranova, Andrew E Davis, Brigid D Lo, Mayumi F Miller, Paul J Paukstelis, Matthew R Swift, Van N Pham, Jesus TorresvazquezAbstract:Objective—Understanding the mechanisms regulating normal and pathological angiogenesis is of great scientific and clinical interest. In this report, we show that mutations in 2 different Aminoacyl-Transfer RNA synthetases, threonyl tRNA synthetase (tarsy58) or isoleucyl tRNA synthetase (iarsy68), lead to similar increased branching angiogenesis in developing zebrafish. Approach and Results—The unfolded protein response pathway is activated by Aminoacyl-Transfer RNA synthetase deficiencies, and we show that unfolded protein response genes atf4, atf6, and xbp1, as well as the key proangiogenic ligand vascular endothelial growth factor (vegfaa), are all upregulated in tarsy58 and iarsy68 mutants. Finally, we show that the protein kinase RNA-like endoplasmic reticulum kinase–activating transcription factor 4 arm of the unfolded protein response pathway is necessary for both the elevated vegfaa levels and increased angiogenesis observed in tarsy58 mutants. Conclusions—Our results suggest that endoplasmic retic...
Matthew R Swift - One of the best experts on this subject based on the ideXlab platform.
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Aminoacyl Transfer RNA synthetase deficiency promotes angiogenesis via the unfolded protein response pathway
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Daniel Castranova, Andrew E Davis, Brigid D Lo, Mayumi F Miller, Paul J Paukstelis, Matthew R Swift, Van N Pham, Jesus TorresvazquezAbstract:Objective—Understanding the mechanisms regulating normal and pathological angiogenesis is of great scientific and clinical interest. In this report, we show that mutations in 2 different Aminoacyl-Transfer RNA synthetases, threonyl tRNA synthetase (tarsy58) or isoleucyl tRNA synthetase (iarsy68), lead to similar increased branching angiogenesis in developing zebrafish. Approach and Results—The unfolded protein response pathway is activated by Aminoacyl-Transfer RNA synthetase deficiencies, and we show that unfolded protein response genes atf4, atf6, and xbp1, as well as the key proangiogenic ligand vascular endothelial growth factor (vegfaa), are all upregulated in tarsy58 and iarsy68 mutants. Finally, we show that the protein kinase RNA-like endoplasmic reticulum kinase–activating transcription factor 4 arm of the unfolded protein response pathway is necessary for both the elevated vegfaa levels and increased angiogenesis observed in tarsy58 mutants. Conclusions—Our results suggest that endoplasmic retic...
Michael T Geraghty - One of the best experts on this subject based on the ideXlab platform.
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congenital visual impairment and progressive microcephaly due to lysyl Transfer ribonucleic acid RNA synthetase kars mutations the expanding phenotype of Aminoacyl Transfer RNA synthetase mutations in human disease
Journal of Child Neurology, 2015Co-Authors: Hugh J Mcmillan, Peter Humphreys, Amanda Smith, Jeremy Schwartzentruber, Pranesh Chakraborty, Dennis E Bulman, Chandree L Beaulieu, Jacek Majewski, Kym M Boycott, Michael T GeraghtyAbstract:Aminoacyl–Transfer ribonucleic acid (RNA) synthetases (ARSs) are a group of enzymes required for the first step of protein translation. Each Aminoacyl–Transfer RNA synthetase links a specific amino acid to its corresponding Transfer RNA component within the cytoplasm, mitochondria, or both. Mutations in ARSs have been linked to a growing number of diseases. Lysyl–Transfer RNA synthetase (KARS) links the amino acid lysine to its cognate Transfer RNA. We report 2 siblings with severe infantile visual loss, progressive microcephaly, developmental delay, seizures, and abnormal subcortical white matter. Exome sequencing identified mutations within the KARS gene (NM_005548.2):c.1312C>T; p.Arg438Trp and c.1573G>A; p.Glu525Lys occurring within a highly conserved region of the catalytic domain. Our patients’ phenotype is remarkably similar to a phenotype recently reported in glutaminyl–Transfer RNA synthetase (QARS), another bifunctional ARS gene. This finding expands the phenotypic spectrum associated with mutati...
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Congenital Visual Impairment and Progressive Microcephaly Due to Lysyl–Transfer Ribonucleic Acid (RNA) Synthetase (KARS) Mutations: The Expanding Phenotype of Aminoacyl–Transfer RNA Synthetase Mutations in Human Disease
Journal of Child Neurology, 2014Co-Authors: Hugh J Mcmillan, Peter Humphreys, Amanda Smith, Jeremy Schwartzentruber, Pranesh Chakraborty, Dennis E Bulman, Chandree L Beaulieu, Jacek Majewski, Kym M Boycott, Michael T GeraghtyAbstract:Aminoacyl–Transfer ribonucleic acid (RNA) synthetases (ARSs) are a group of enzymes required for the first step of protein translation. Each Aminoacyl–Transfer RNA synthetase links a specific amino acid to its corresponding Transfer RNA component within the cytoplasm, mitochondria, or both. Mutations in ARSs have been linked to a growing number of diseases. Lysyl–Transfer RNA synthetase (KARS) links the amino acid lysine to its cognate Transfer RNA. We report 2 siblings with severe infantile visual loss, progressive microcephaly, developmental delay, seizures, and abnormal subcortical white matter. Exome sequencing identified mutations within the KARS gene (NM_005548.2):c.1312C>T; p.Arg438Trp and c.1573G>A; p.Glu525Lys occurring within a highly conserved region of the catalytic domain. Our patients’ phenotype is remarkably similar to a phenotype recently reported in glutaminyl–Transfer RNA synthetase (QARS), another bifunctional ARS gene. This finding expands the phenotypic spectrum associated with mutati...