Abstract
Kidney cysts are characterized by an abnormal tubular geometry that may result from loss of orientation and random cell divisions during renal development. Since cystic kidney disease is caused by mutations of ciliary proteins and cilia act as flow sensors in the kidney, we examined three polarized events in Madin Darby Canine Kidney cells under flow: cell division, cell migration, and centriole movement. We found that the mitotic orientation of dividing cells was not affected by flow and was randomly distributed in relation to the direction of the flow. Flow did not alter the direction and speed of cell migration in a wound-healing assay. However, flow resulted in increased motility of centrioles and biased centrioles to move along the axis of the flow. This effect was lost after flow-induced calcium signaling was abolished by a mutant polycystin 2. Our findings suggest that the cilium may translate fluid flow into altered centriole movements to provide tubular epithelial cells with the spatial orientation required to establish and/or maintain a normal tubular geometry.
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Abbreviations
- ADPKD:
-
autosomal dominant polycystic kidney disease
- ARPKD:
-
autosomal recessive PKD
- BBS:
-
Bardet Biedl Syndrome
- NPHP:
-
nephronophthisis
- MDCK:
-
Madin Darby Canine Kidney
- PCP:
-
planar cell polarity
- YFP:
-
yellow fluorescent protein
- GFP:
-
green fluorescent protein
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Acknowledgements
We thank Simone Braeg for expert technical assistance. We thank Yuko Mimori-Kiyosue for the EB1.GFP construct and A. Miyawaki for the YFP variant Venus. We thank the members of the Renal Unit for helpful discussions. This work was funded by DFG WA597 (GW) and SFB 592 Z2 (RN).
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Kotsis, F., Nitschke, R., Doerken, M. et al. Flow modulates centriole movements in tubular epithelial cells. Pflugers Arch - Eur J Physiol 456, 1025–1035 (2008). https://doi.org/10.1007/s00424-008-0475-8
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DOI: https://doi.org/10.1007/s00424-008-0475-8