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
-
- Zebrafish Proteins/deficiency*
- Zebrafish Proteins/genetics
- Signal Transduction
- Genotype
- Threonine-tRNA Ligase/deficiency*
- Threonine-tRNA Ligase/genetics
- Activating Transcription Factor 6/genetics
- Activating Transcription Factor 6/metabolism
- Zebrafish
- Regulatory Factor X Transcription Factors
- Phenotype
- Mutation
- Activating Transcription Factor 4/genetics
- Activating Transcription Factor 4/metabolism
- Endoplasmic Reticulum/metabolism
- Gene Expression Regulation, Developmental
- Neovascularization, Physiologic*
- Unfolded Protein Response*
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Endoplasmic Reticulum Stress
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Animals, Genetically Modified
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Animals
- Isoleucine-tRNA Ligase/deficiency*
- Isoleucine-tRNA Ligase/genetics
- X-Box Binding Protein 1
- 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