PUBLICATION
Aminoacyl-Transfer RNA Synthetase Deficiency Promotes Angiogenesis via the Unfolded Protein Response Pathway
- Authors
- Castranova, D., Davis, A.E., Lo, B.D., Miller, M.F., Paukstelis, P.J., Swift, M.R., Pham, V.N., Torres-Vázquez, J., Bell, K., Shaw, K.M., Kamei, M., Weinstein, B.M.
- ID
- ZDB-PUB-160130-9
- Date
- 2016
- Source
- Arteriosclerosis, Thrombosis, and Vascular Biology 36(4): 655-62 (Journal)
- Registered Authors
- Castranova, Dan, Davis, Andrew, Kamei, Makoto, Lo, Brigid, Miller, Mayumi, Pham, Van, Swift, Matthew Russell, Weinstein, Brant M.
- Keywords
- endoplasmic reticulum, protein kinases, unfolded protein response, vascular endothelial growth factor A, zebrafish
- MeSH Terms
-
- Endoplasmic Reticulum Stress
- Animals, Genetically Modified
- Neovascularization, Physiologic*
- Threonine-tRNA Ligase/deficiency*
- Threonine-tRNA Ligase/genetics
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Regulatory Factor X Transcription Factors
- X-Box Binding Protein 1
- Activating Transcription Factor 6/genetics
- Activating Transcription Factor 6/metabolism
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Animals
- Zebrafish
- Activating Transcription Factor 4/genetics
- Activating Transcription Factor 4/metabolism
- Genotype
- Gene Expression Regulation, Developmental
- Isoleucine-tRNA Ligase/deficiency*
- Isoleucine-tRNA Ligase/genetics
- Phenotype
- Zebrafish Proteins/deficiency*
- Zebrafish Proteins/genetics
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Unfolded Protein Response*
- Endoplasmic Reticulum/metabolism
- Signal Transduction
- Mutation
- PubMed
- 26821951 Full text @ Arterio., Thromb., and Vas. Bio.
Citation
Castranova, D., Davis, A.E., Lo, B.D., Miller, M.F., Paukstelis, P.J., Swift, M.R., Pham, V.N., Torres-Vázquez, J., Bell, K., Shaw, K.M., Kamei, M., Weinstein, B.M. (2016) Aminoacyl-Transfer RNA Synthetase Deficiency Promotes Angiogenesis via the Unfolded Protein Response Pathway. Arteriosclerosis, Thrombosis, and Vascular Biology. 36(4):655-62.
Abstract
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 (tars(y58)) or isoleucyl tRNA synthetase (iars(y68)), 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 tars(y58) and iars(y68) 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 tars(y58) mutants.
Conclusions Our results suggest that endoplasmic reticulum stress acts as a proangiogenic signal via unfolded protein response pathway-dependent upregulation of vegfaa.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping