title: Colocalization of the (Pro)renin Receptor/Atp6ap2 with H+-ATPases in Mouse Kidney but Prorenin Does Not Acutely Regulate Intercalated Cell H+-ATPase Activity.
abstract: The (Pro)renin receptor (P)RR/Atp6ap2 is a cell surface protein capable of binding and non-proteolytically activate prorenin. Additionally, (P)RR is associated with H(+)-ATPases and alternative functions in H(+)-ATPase regulation as well as in Wnt signalling have been reported. Kidneys express very high levels of H(+)-ATPases which are involved in multiple functions such as endocytosis, membrane protein recycling as well as urinary acidification, bicarbonate reabsorption, and salt absorption. Here, we wanted to localize the (P)RR/Atp6ap2 along the murine nephron, exmaine whether the (P)RR/Atp6ap2 is coregulated with other H(+)-ATPase subunits, and whether acute stimulation of the (P)RR/Atp6ap2 with prorenin regulates H(+)-ATPase activity in intercalated cells in freshly isolated collecting ducts. We localized (P)PR/Atp6ap2 along the murine nephron by qPCR and immunohistochemistry. (P)RR/Atp6ap2 mRNA was detected in all nephron segments with highest levels in the collecting system coinciding with H(+)-ATPases. Further experiments demonstrated expression at the brush border membrane of proximal tubules and in all types of intercalated cells colocalizing with H(+)-ATPases. In mice treated with NH4Cl, NaHCO3, KHCO3, NaCl, or the mineralocorticoid DOCA for 7 days, (P)RR/Atp6ap2 and H(+)-ATPase subunits were regulated but not co-regulated at protein and mRNA levels. Immunolocalization in kidneys from control, NH4Cl or NaHCO3 treated mice demonstrated always colocalization of PRR/Atp6ap2 with H(+)-ATPase subunits at the brush border membrane of proximal tubules, the apical pole of type A intercalated cells, and at basolateral and/or apical membranes of non-type A intercalated cells. Microperfusion of isolated cortical collecting ducts and luminal application of prorenin did not acutely stimulate H(+)-ATPase activity. However, incubation of isolated collecting ducts with prorenin non-significantly increased ERK1/2 phosphorylation. Our results suggest that the PRR/Atp6ap2 may form a complex with H(+)-ATPases in proximal tubule and intercalated cells but that prorenin has no acute effect on H(+)-ATPase activity in intercalated cells.
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Daryadel
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Soline
authors.initials: S
authors.lastname: Bourgeois
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Marta F L
authors.initials: MF
authors.lastname: Figueiredo
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Ana
authors.initials: A
authors.lastname: Gomes Moreira
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Nicole B
authors.initials: NB
authors.lastname: Kampik
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Oberli
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.|Divison of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Nilufar
authors.initials: N
authors.lastname: Mohebbi
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Lu
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Meima
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.affiliation: Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Wagner
mesh_terms: D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D051399:Aquaporin 2 / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D005786:Gene Expression Regulation; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007679:Kidney Medulla / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D006180:Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction; D017693:Sodium Bicarbonate / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1 / Q000235:genetics / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics / Q000378:metabolism; D000076988:Sulfate Transporters; D000093342:Prorenin Receptor; D000098853:Podoplanin
chemical_list: D000643:Ammonium Chloride; D027321:Anion Transport Proteins; D051399:Aquaporin 2; D008562:Membrane Glycoproteins; D006180:Proton-Translocating ATPases; D011956:Receptors, Cell Surface; D012083:Renin; D017693:Sodium Bicarbonate; D012965:Sodium Chloride; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D064466:Solute Carrier Family 12, Member 1; D064486:Solute Carrier Family 12, Member 3; D000076988:Sulfate Transporters; C583530:ATP6AP2 protein, mouse; D000093342:Prorenin Receptor; C496024:Aqp2 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C578715:Slc12a1 protein, mouse; C578875:Slc12a3 protein, mouse; C494849:Slc26a4 protein, mouse; C493555:Slc34a1 protein, mouse
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