Fol. Biol. 2015, 61, 168-177

https://doi.org/10.14712/fb2015061050168

Prorenin Receptor Homologue VHA-20 is Critical for Intestinal pH Regulation, Ion and Water Management and Larval Development in

V. Zima1, K. Šebková1, K. Šimečková1, T. Dvořák1, V. Saudek2, Marta Kostrouchová1

1Institute Of Cellular Biology And Pathology, First Faculty Of Medicine, Charles University In Prague, Czech Republic
2University Of Cambridge Metabolic Research Laboratories, Wellcome Trust–Medical Research Council Institute Of Metabolic Science, Cambridge, United Kingdom

Received May 2015
Accepted June 2015

The prorenin receptor (ATP6AP2) is a multifunctional transmembrane protein; it is a constituent of proton-translocating V-ATPase, a non-proteolytic activator of renin and an adaptor in the Wnt/ β-catenin pathway. Here, we studied vha-20, one of the two prorenin receptor homologues that are identified by sequence similarity in the C. elegans genome. We show that vha-20 (R03E1.2) is prominently expressed in the intestine, in the excretory cell and in amphid neurons, tissues critical for regulation of ion and water management. The expression of vha-20 in the intestine is dependent on NHR-31, a nuclear receptor related to HNF4. VHA-20 is indispensable for normal larval development, acidification of the intestine, and is required for nutrient uptake. Inhibition of vha-20 by RNAi leads to complex deterioration of water and pH gradients at the level of the whole organism including distention of pseudocoelome cavity. This suggests new roles of prorenin receptor in the regulation of body ion and water management and in acidification of intestinal lumen in nematodes.

Funding

The main funding sources were: 1/ the European Regional Development Fund “BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University in Vestec” (CZ.1.05/1.1.00/02.0109) (Start-Up Grant to the group Structure and Function of Cells in Their Normal State and in Pathology – Integrative Biology and Pathology); 2/ grant PRVOUK-P27/LF1/1 from Charles University in Prague; 3/ grants SVV 260023/2014 and SVV 260149/2015 from Charles University in Prague. MK contributed with personal funds to this work. KŠeb. was partially supported by grant 579612 from Charles University in Prague. KŠim. was partially supported by grant UNCE 204022 from Charles University in Prague. MK obtained partial support from project P302/12/G157 from the Czech Science Foundation. The funders (except MK) had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

43 live references