PUBLICATION
Duplicated zebrafish (Danio rerio) inositol phosphatases inpp5ka and inpp5kb diverged in expression pattern and function
- Authors
- Shukla, D., Gural, B.M., Cauley, E.S., Battula, N., Mowla, S., Karas, B.F., Roberts, L.E., Cavallo, L., Turkalj, L., Moody, S.A., Swan, L.E., Manzini, M.C.
- ID
- ZDB-PUB-230516-32
- Date
- 2023
- Source
- Development genes and evolution 233(1): 25-34 (Journal)
- Registered Authors
- Keywords
- Gene duplication, INPP5K, Inositol phosphatase, Zebrafish
- MeSH Terms
-
- Animals
- Gene Expression Regulation*
- Humans
- Inositol
- Mutation
- Phosphoric Monoester Hydrolases/genetics
- Phosphoric Monoester Hydrolases/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 37184573 Full text @ Dev. Genes Evol.
Citation
Shukla, D., Gural, B.M., Cauley, E.S., Battula, N., Mowla, S., Karas, B.F., Roberts, L.E., Cavallo, L., Turkalj, L., Moody, S.A., Swan, L.E., Manzini, M.C. (2023) Duplicated zebrafish (Danio rerio) inositol phosphatases inpp5ka and inpp5kb diverged in expression pattern and function. Development genes and evolution. 233(1):25-34.
Abstract
One hurdle in the development of zebrafish models of human disease is the presence of multiple zebrafish orthologs resulting from whole genome duplication in teleosts. Mutations in inositol polyphosphate 5-phosphatase K (INPP5K) lead to a syndrome characterized by variable presentation of intellectual disability, brain abnormalities, cataracts, muscle disease, and short stature. INPP5K is a phosphatase acting at position 5 of phosphoinositides to control their homeostasis and is involved in insulin signaling, cytoskeletal regulation, and protein trafficking. Previously, our group and others have replicated the human phenotypes in zebrafish knockdown models by targeting both INPP5K orthologs inpp5ka and inpp5kb. Here, we show that inpp5ka is the more closely related orthologue to human INPP5K. While both inpp5ka and inpp5kb mRNA expression levels follow a similar trend in the developing head, eyes, and tail, inpp5ka is much more abundantly expressed in these tissues than inpp5kb. In situ hybridization revealed a similar trend, also showing unique localization of inpp5kb in the pineal gland and retina indicating different transcriptional regulation. We also found that inpp5kb has lost its catalytic activity against its preferred substrate, PtdIns(4,5)P2. Since most human mutations are missense changes disrupting phosphatase activity, we propose that loss of inpp5ka alone can be targeted to recapitulate the human presentation. In addition, we show that the function of inpp5kb has diverged from inpp5ka and may play a novel role in the zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping