Duplicated zebrafish (Danio rerio) inositol phosphatases inpp5ka and inpp5kb diverged in expression pattern and function.
Dhyanam Shukla, Brian M Gural, Edmund S Cauley, Namarata Battula, Shorbon Mowla, Brittany F Karas, Llion E Roberts, Luca Cavallo, Luka Turkalj, Sally A Moody, Laura E Swan, M Chiara Manzini
Author Information
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.
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 INPP5K. and INPP5K.. Here, we show that INPP5K. is the more closely related orthologue to humanINPP5K. While both INPP5K. and INPP5K. mRNA expression levels follow a similar trend in the developing head, eyes, and tail, INPP5K. is much more abundantly expressed in these tissues than INPP5K.. In situ hybridization revealed a similar trend, also showing unique localization of INPP5K. in the pineal gland and retina indicating different transcriptional regulation. We also found that INPP5K. 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 INPP5K. alone can be targeted to recapitulate the human presentation. In addition, we show that the function of INPP5K. has diverged from INPP5K. and may play a novel role in the zebrafish.
