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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Soc+Nephrol
2015 ; 26
(6
): 1269-78
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Short-term functional adaptation of aquaporin-1 surface expression in the
proximal tubule, a component of glomerulotubular balance
#MMPMID25270072
Pohl M
; Shan Q
; Petsch T
; Styp-Rekowska B
; Matthey P
; Bleich M
; Bachmann S
; Theilig F
J Am Soc Nephrol
2015[Jun]; 26
(6
): 1269-78
PMID25270072
show ga
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.