FIGURE

Fig. 6

ID
ZDB-FIG-211101-36
Publication
Zhang et al., 2021 - Selective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis
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Fig. 6

A summary of the study and the working model for the selective and competitive functions of AAR and UPR pathways.

The close interconnection of the AAR and UPR pathways makes it difficult to distinguish between them, therefore the angiogenesis induced by aaRS deficiency has been assumptively attributed to activation of both pathways. While UPR has been addressed in previous studies, it is unclear whether AAR is also activated and whether both are required in this process (left panel). We established that these highly interconnected pathways can be distinguished in the herein-generated zebrafish angiogenic model that harbors a tars mutation, by using an approach combining systematic gene expression profiling and quantitative phenotypic analysis upon a variety of genetic and pharmacological manipulations of these pathways (middle panel). We found that AAR, but not UPR, is activated and is functionally required for the angiogenic phenotypes in the tars mutants (right panel). Notably, while Perk-mediated UPR is inactive in the tars mutants, it plays an important role in normal development; however, the function of Perk is overwhelmed by Gcn2 in the stress condition, through competing for phosphorylation of their shared target, eIF2α. The phosphorylated eIF2α (p-eIF2α) by Gcn2 and Perk can be distinguished by the cells/organisms (therefore illustrated in different colors) and thus regulate the partially overlapped AAR- and UPR-associated genes. The question marks denote the possible cause, mechanism, and functional consequence of UPR, which should be different from those of AAR as addressed in this study.

Expression Data

Expression Detail
Antibody Labeling
Phenotype Data

Phenotype Detail
Acknowledgments
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