title: Short-term functional adaptation of aquaporin-1 surface expression in the proximal tubule, a component of glomerulotubular balance.
abstract: Transepithelial water flow across the renal proximal tubule is mediated predominantly by aquaporin-1 (AQP1). Along this nephron segment, luminal delivery and transepithelial reabsorption are directly coupled, a phenomenon called glomerulotubular balance. We hypothesized that the surface expression of AQP1 is regulated by fluid shear stress, contributing to this effect. Consistent with this finding, we found that the abundance of AQP1 in brush border apical and basolateral membranes was augmented >2-fold by increasing luminal perfusion rates in isolated, microperfused proximal tubules for 15 minutes. Mouse kidneys with diminished endocytosis caused by a conditional deletion of megalin or the chloride channel ClC-5 had constitutively enhanced AQP1 abundance in the proximal tubule brush border membrane. In AQP1-transfected, cultured proximal tubule cells, fluid shear stress or the addition of cyclic nucleotides enhanced AQP1 surface expression and concomitantly diminished its ubiquitination. These effects were also associated with an elevated osmotic water permeability. In sum, we have shown that luminal surface expression of AQP1 in the proximal tubule brush border membrane is regulated in response to flow. Cellular trafficking, endocytosis, an intact endosomal compartment, and controlled protein stability are the likely prerequisites for AQP1 activation by enhanced tubular fluid shear stress, serving to maintain glomerulotubular balance.
authors.affiliation: Institute of Anatomy, Charité Universitätsmedizin, Berlin, Germany;
authors.forename: Marcus
authors.initials: M
authors.lastname: Pohl
authors.affiliation: Institute of Physiology, Kiel University, Kiel, Germany;
authors.forename: Qixian
authors.initials: Q
authors.lastname: Shan
authors.affiliation: Institute of Anatomy, Charité Universitätsmedizin, Berlin, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Petsch
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland; and.
authors.forename: Beata
authors.initials: B
authors.lastname: Styp-Rekowska
authors.affiliation: Institute of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Matthey
authors.affiliation: Institute of Physiology, Kiel University, Kiel, Germany;
authors.forename: Markus
authors.initials: M
authors.lastname: Bleich
authors.affiliation: Institute of Anatomy, Charité Universitätsmedizin, Berlin, Germany;
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.affiliation: Institute of Anatomy, Charité Universitätsmedizin, Berlin, Germany; Institute of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland franziska.theilig@unifr.ch.
authors.forename: Franziska
authors.initials: F
authors.lastname: Theilig
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008871:Microvilli / Q000378:metabolism; D009995:Osmosis; D021381:Protein Transport / Q000502:physiology; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013997:Time Factors; D014882:Water-Electrolyte Balance / Q000235:genetics* / Q000502:physiology
chemical_list: C496021:Aqp1 protein, mouse; D051398:Aquaporin 1
keywords: cell and transport physiology; renal proximal tubule cell; water channels; water transport