Hypertonicity is involved in redirecting the aquaporin-2 water channel into the basolateral, instead of the apical, plasma membrane of renal epithelial cells.
In renal collecting ducts, vasopressin increases the expression of and redistributes aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical membrane, leading to urine concentration. However, basolateral membrane expression of AQP2, in addition to AQP3 and AQP4, is often detected in inner medullary principal cells in vivo. Here, potential mechanisms that regulate apical versus basolateral targeting of AQP2 were examined. The lack of AQP2-4 association into heterotetramers and the complete apical expression of AQP2 when highly expressed in Madin-Darby canine kidney cells indicated that neither heterotetramerization of AQP2 with AQP3 and/or AQP4, nor high expression levels of AQP2 explained the basolateral AQP2 localization. However, long term hypertonicity, a feature of the inner medullary interstitium, resulted in an insertion of AQP2 into the basolateral membrane of Madin-Darby canine kidney cells after acute forskolin stimulation. Similarly, a marked insertion of AQP2 into the basolateral membrane of principal cells was observed in the distal inner medulla from normal rats and Brattleboro rats after acute vasopressin treatment of tissue slices that had been chronically treated with vasopressin to increase interstitial osmolality in the medulla, but not in tissues from vasopressin-deficient Brattleboro rats. These data reveal for the first time that chronic hypertonicity can program cells in vitro and in vivo to change the insertion of a protein into the basolateral membrane instead of the apical membrane.
van Balkom
Bas W M
BW
Department of Cell Physiology, Nijmegen Center for Molecular Life Sciences, UMC St. Radboud, The Netherlands.
van Raak
Marcel
M
Breton
Sylvie
S
Pastor-Soler
Nuria
N
Bouley
Richard
R
van der Sluijs
Peter
P
Brown
Dennis
D
Deen
Peter M T
PM
D000818:Animals; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins / Q000032:analysis* / Q000737:chemistry; D001127:Arginine Vasopressin; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry*; D004847:Epithelial Cells / Q000737:chemistry; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry*; D007679:Kidney Medulla / Q000737:chemistry; D051381:Rats; D012462:Saline Solution, Hypertonic
C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; C496032:Aqp4 protein, rat; D051399:Aquaporin 2; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins; D012462:Saline Solution, Hypertonic; D001127:Arginine Vasopressin; D051400:Aquaporin 3