Mechanosensory function of microvilli of the kidney proximal tubule

Abstract

Normal variations in glomerular filtration induce proportional changes in proximal tubule Na ؉ reabsorption. This ''glomerulotubular balance'' derives from flow dependence of Na ؉ uptake across luminal cell membranes; however, the underlying physical mechanism is unknown. Our hypothesis is that flow-dependent reabsorption is an autoregulatory mechanism that is independent of neural and hormonal systems. It is signaled by the hydrodynamic torque (bending moment) on epithelial microvilli. Such signals need to be transmitted to the terminal web to modulate Na ؉ -H ؉ -exchange activity. To investigate this hypothesis, we examined Na ؉ transport and tubular diameter in response to different flow rates during the microperfusion of isolated S2 proximal tubules from mouse kidneys. The data were analyzed by using a mathematical model to estimate the microvillous torque as function of flow. In this model, increases in luminal diameter have the effect of blunting the impact of flow velocity on microvillous shear stress and, thus, microvillous torque. We found that variations in microvillous torque produce nearly identical fractional changes in Na ؉ reabsorption. Furthermore, the flow-dependent Na ؉ transport is increased by increasing luminal fluid viscosity, diminished in Na ؉ -H ؉ exchanger isoform 3 knockout mice, and abolished by nontoxic disruption of the actin cytoskeleton. These data support our hypothesis that the ''brush-border'' microvilli serve a mechanosensory function in which fluid dynamic torque is transmitted to the actin cytoskeleton and modulates Na ؉ absorption in kidney proximal tubules. glomerulotubular balance ͉ flow-dependent transport ͉ Na ϩ -H ϩ exchange

Short-Term Functional Adaptation of Aquaporin-1 Surface Expression in the Proximal Tubule, a Component of Glomerulotubular Balance

“…22 Absence of the main proximal tubular sodium transporter, NHE3, or the principal water channel, AQP1, did not entirely abolish GTB but significantly reduced the slope of flow-dependent volume absorption. 16,18,23,24 We aimed to resolve whether the surface expression of AQP1 may be altered in the short term by inducing changes in luminal flow rate and FSS. The selected flow rates for the isolated, microperfused tubules reflected the end proximal physiologic range of 5-30 nl/min.…”

“…These diameters correspond to flow rates of ,5 and .25 nl/min. 17,18 Duration of the perfusion was 15 minutes throughout. Morphologic analysis revealed an intact structure of the tubules in both conditions ( Figure 1, A and B).…”

HE6/GPR64 adhesion receptor co-localizes with apical and subapical F-actin scaffold in male excurrent duct epithelia

“…This dual structure probably comprised the apical microvillar brush border plus underlying subapical cytoskeleton. It was hypothesized that microvilli function as sensors to detect and amplify hydrodynamic forces and transmit them to the subapical actin cytoskeleton (Du et al 2004). The present results on the subcellular distribution of the HE6/GPR64 receptor and its co-localization with F-actin are compatible with such sensor function.…”

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

“…Interestingly, a mechanosensory function has also been postulated for another class of cells with espin-containing microvilli: epithelial cells in renal proximal tubule [12]. In this case, an increase in the hydrodynamic torque on the microvilli is believed to increase the efficiency of absorption of Na + to maintain glomerulotubular balance [56]. Kidney epithelial cells are appear to be able to sense flow via their primary cilia, deformation of which causes increases in intracellular Ca 2+ [57].…”