title: Flow modulates centriole movements in tubular epithelial cells.
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.
authors.affiliation: Department of Medicine, Renal Unit, University Hospital Freiburg, 79106, Freiburg, Germany.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Kotsis
authors.forename: Roland
authors.initials: R
authors.lastname: Nitschke
authors.forename: Mara
authors.initials: M
authors.lastname: Doerken
authors.forename: Gerd
authors.initials: G
authors.lastname: Walz
authors.forename: E Wolfgang
authors.initials: EW
authors.lastname: Kuehn
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002502:Centrioles / Q000502:physiology* / Q000648:ultrastructure; D018385:Centrosome / Q000502:physiology; D002923:Cilia / Q000502:physiology / Q000648:ultrastructure; D003595:Cytoplasmic Streaming / Q000502:physiology*; D015194:Diffusion Chambers, Culture; D004285:Dogs; D004847:Epithelial Cells / Q000502:physiology* / Q000648:ultrastructure; D005456:Fluorescent Dyes; D016257:Fura-2; D007202:Indicators and Reagents; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009399:Nephrons / Q000166:cytology / Q000502:physiology; D010957:Plasmids / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D011506:Proteins; D016257:Fura-2