Duplicated zebrafish (Danio rerio) inositol phosphatases inpp5ka and inpp5kb diverged in expression pattern and function

Authors

Dhyanam Shukla, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA.
Brian M. Gural, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA.
Edmund S. Cauley, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Namarata Battula, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA.
Shorbon Mowla, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA.
Brittany F. Karas, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA.
Llion E. Roberts, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Luca Cavallo, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA.
Luka Turkalj, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA.
Sally A. Moody, Department of Anatomy and Cell Biology, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
Laura E. Swan, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
M Chiara Manzini, Department of Neuroscience and Cell Biology and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, CHINJ Rm 3274, New Brunswick, NJ, 08901, USA. chiara.manzini@rutgers.edu.

Document Type

Journal Article

Publication Date

6-1-2023

Journal

Development genes and evolution

Volume

233

Issue

1

DOI

10.1007/s00427-023-00703-z

Keywords

Gene duplication; INPP5K; Inositol phosphatase; Zebrafish

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)P. 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.

APA Citation

Shukla, Dhyanam; Gural, Brian M.; Cauley, Edmund S.; Battula, Namarata; Mowla, Shorbon; Karas, Brittany F.; Roberts, Llion E.; Cavallo, Luca; Turkalj, Luka; Moody, Sally A.; Swan, Laura E.; and Manzini, M Chiara, "Duplicated zebrafish (Danio rerio) inositol phosphatases inpp5ka and inpp5kb diverged in expression pattern and function" (2023). GW Authored Works. Paper 2808.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2808

Department

Anatomy and Regenerative Biology