PUBLICATION
IMPDH forms the cytoophidium in zebrafish
- Authors
- Keppeke, G.D., Chang, C.C., Antos, C.L., Peng, M., Sung, L.Y., Coelho Andrade, L.E., Liu, J.L.
- ID
- ZDB-PUB-210529-13
- Date
- 2021
- Source
- Developmental Biology 478: 89-101 (Journal)
- Registered Authors
- Antos, Christopher
- Keywords
- Adult zebrafish, Cytoophidium, IMPDH, Larval zebrafish
- MeSH Terms
-
- Animals
- Cell Line
- Cytoplasmic Structures/chemistry
- Cytoplasmic Structures/ultrastructure*
- Gene Expression
- Guanosine Triphosphate/biosynthesis
- Guanosine Triphosphate/metabolism
- Humans
- IMP Dehydrogenase/chemistry*
- IMP Dehydrogenase/genetics
- IMP Dehydrogenase/metabolism
- Isoenzymes/chemistry
- Isoenzymes/genetics
- Point Mutation
- Up-Regulation
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 34048735 Full text @ Dev. Biol.
Citation
Keppeke, G.D., Chang, C.C., Antos, C.L., Peng, M., Sung, L.Y., Coelho Andrade, L.E., Liu, J.L. (2021) IMPDH forms the cytoophidium in zebrafish. Developmental Biology. 478:89-101.
Abstract
Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in de novo guanine nucleotide biosynthesis. Its activity is negatively regulated by the binding of GTP. IMPDH can form a membraneless subcellular structure termed the cytoophidium in response to certain changes in the metabolic status of the cell. The polymeric form of IMPDH, which is the subunit of the cytoophidium, has been shown to be more resistant to the inhibition by GTP at physiological concentrations, implying a functional correlation between cytoophidium formation and the upregulation of GTP biosynthesis. Herein we demonstrate that zebrafish IMPDH1b and IMPDH2 isoforms can assemble abundant cytoophidium in most of cultured cells under stimuli, while zfIMPDH1a shows distinctive properties of forming the cytoophidium in different cell types. Point mutations that disrupt cytoophidium structure in mammalian models also prevent the aggregation of zebrafish IMPDHs. In addition, we discover the presence of the IMPDH cytoophidium in various tissues of larval and adult fish under normal growth conditions. Our results reveal that polymerization and cytoophidium assembly of IMPDH could be a regulatory machinery conserved among vertebrates, and with specific physiological purposes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping