Unanticipated domain requirements for < i > Drosophila < /i > Wnk kinase < i > in vivo < /i >

by Prathibha Yarikipati, Sima Jonusaite, John M. Pleinis, Carihann Dominicci Cotto, David Sanchez-Hernandez, Daryl E. Morrison, Suhani Goyal, Jeffery Schellinger, Clothilde P énalva, Jennifer Curtiss, Aylin R. Rodan, Andreas Jenny WNK (With no Lysine [K]) kinases have critical roles in the maintenance of ion homeostasis and the regulation of cell volume. Their overactivation leads to pseudohypoaldosteronism type II (Gordon syndrome) characterized by hyperkalemia and high blood pressure. More recently, WNK family members have been shown to be required for the development of the nervous system in mice, zebrafish, and flies, and the cardiovascular system of mice and fish. Furthermore, human WNK2 andDrosophila Wnk modulate canonical Wnt signaling. In addition to a well-conserved kinase domain, animal WNKs have a large, poorly conserved C-terminal domain whose function has been largely mysterious. In most but not all cases, WNKs bind and activate downstream kinases OSR1/SPAK, which in turn regulate the activity of various ion transporters and channels. Here, we show thatDrosophila Wnk regulates Wnt signaling and cell size during the development of the wing in a manner dependent on Fray, the fly homolog of OSR1/SPAK. We show that the only canonical RF(X)V/I motif of Wnk, thought to be essential for WNK interactions with OSR1/SPAK, is required to interact with Frayin vitro. However, this motif is unexpectedly dispensable for Fray-dependent Wnk functionsin vivo during fly developme...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research