The renal cell primary cilium functions as a flow sensor

Praetorius, Helle A.; Spring, Kenneth R.

doi:10.1097/00041552-200309000-00006

Cited by 242 publications

(171 citation statements)

References 20 publications

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“…Although the linear dependence of reabsorption on microvillous torque is reassuring, this issue is difficult to resolve with certainty because of the positive correlation of hydrodynamic drag on both microvilli and cilia. Our data show that increased torques on the microvilli produced a stimulation of Na ϩ transport, whereas the torques on the cilia should lead to a decrease in absorption because the bending of the cilia causes an increase in intracellular Ca 2ϩ through stretchactivated ion channels (28). The increased intracellular Ca 2ϩ will produce an inhibition of Na ϩ and HCO 3 Ϫ absorption in proximal tubules (30).…”

Section: Discussionmentioning

confidence: 73%

“…In contrast to the mechanosensory function of microvilli proposed for the proximal nephron, flow-dependent transport in the distal nephron has recently been attributed to renal epithelial cilia (28). Subsequently, Liu et al (29) demonstrated that flowdependent increases in [Ca 2ϩ ] i occur in both principal cells with apical cilia and intercalated cells with apical microvilli or microplicae that lack cilia, suggesting that these intercalated cell projections also serve a mechanosensory function.…”

Section: Discussionmentioning

confidence: 99%

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Mechanosensory function of microvilli of the kidney proximal tubule

Duan

Yan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

104

128

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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

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Mechanosensory function of microvilli of the kidney proximal tubule

Duan

Yan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

104

128

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show abstract

“…While the exact function of the immotile, primary cilium of kidney epithelial cells is not well understood, it is now well established that loss of ciliary function and/or formation results in cystic diseases pointing to a central role of this organelle in PKD pathophysiology [50,51]. Because cilia function as sensory organelles in the olfactory and vision systems [52], it is believed it may have a similar sensory function in the renal epithelial cells [53,54]. Such a function could be fluid flow sensing [54].…”

Section: Function At the Primary Ciliummentioning

confidence: 99%

“…Because cilia function as sensory organelles in the olfactory and vision systems [52], it is believed it may have a similar sensory function in the renal epithelial cells [53,54]. Such a function could be fluid flow sensing [54]. In support of this hypothesis, it has been shown that mechanical bending of the primary cilium or fluid flow in MDCK cells resulted in increases in intracellular Ca 2+ concentration which was dependent on extracellular Ca 2+ , PLC activation and inositol 1,4,5 trisphosphate (IP 3 )-induced release of intracellular Ca 2+ stores [55][56][57].…”

Section: Function At the Primary Ciliummentioning

confidence: 99%

Cell biology of polycystin-2

Tsiokas¹,

Kim²,

Ong³

2007

Cellular Signalling

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Naturally occurring mutations in two separate, but interacting loci, pkd1 and pkd2 are responsible for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is one of the most common genetic diseases resulting primarily in the formation of large kidney, liver, and pancreatic cysts. Homozygous deletion of either pkd1 or pkd2 results in embryonic lethality in mice due to kidney and heart defects illustrating their indispensable roles in mammalian development. However, the mechanism by which mutations in these genes cause ADPKD and other developmental defects are unknown. Research in the past several years has revealed that PKD2 has multiple functions depending on its subcellular localization. It forms a receptor-operated, non-selective cation channel in the plasma membrane, a novel intracellular Ca 2+ release channel in the endoplasmic reticulum (ER), and a mechanosensitive channel in the primary cilium. This review focuses on the functional compartmentalization of PKD2, its modes of activation, and PKD2-mediated signal transduction.

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“…Cilia serve as a cell's "antenna" to sample a broad range of extracellular signals in olfaction, vision, taste, and mechanosensation (4,5). Primary cilia of kidney epithelia are mechanosensitive, detecting fluid flow through the tubule (6). Cilia of olfactory epithelia distinguish a large number of odorants (7).…”

mentioning

confidence: 99%

Heterotrimeric Kinesin-2 (KIF3) Mediates Transition Zone and Axoneme Formation of Mouse Photoreceptors

Jiang

Wei

Ronquillo

et al. 2015

Journal of Biological Chemistry

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Background: Heterotrimeric kinesin-2 (KIF3) has been implicated in intraflagellar trafficking of photoreceptor membrane proteins by IFT. Results: KIF3 and IFT88 are required for transition zone and axoneme formation, but are dispensable for rhodopsin trafficking. Conclusion: Transmembrane proteins, including rhodopsin, traffic to the OS even when IFT is disabled. Significance: KIF3 builds and maintains the photoreceptor transition zone and axoneme that are essential for photoreceptor integrity and vision.

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The renal cell primary cilium functions as a flow sensor

Abstract: The primary cilium is mechanically sensitive and serves as a flow sensor in cultured renal epithelia. Bending the cilium by mechanical means or flow causes a large, prolonged transient increase in intracellular calcium. The mechanically sensitive protein in the cilium is a polycystin.

Cited by 242 publications

References 20 publications

Mechanosensory function of microvilli of the kidney proximal tubule

Mechanosensory function of microvilli of the kidney proximal tubule

Cell biology of polycystin-2

Heterotrimeric Kinesin-2 (KIF3) Mediates Transition Zone and Axoneme Formation of Mouse Photoreceptors

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