Cilia movement regulates expression of the Raf-1 kinase inhibitor protein.

Academic Article

Abstract

  • Renal epithelial cell primary cilia act as mechanosensors in response to changes in luminal fluid flow. To determine the role of cilia bending in the mechanosensory function of cilia, we performed proteomic analysis of collecting duct cell lines with or without cilia that were kept stationary or rotated to stimulate cilia bending. Expression of the Raf-1 kinase inhibitor protein (RKIP), an inhibitor of the MAPK pathway, was significantly elevated in rotated cilia (+) cells. This was compared with RKIP levels in cilia (-) cells that were stationary or rotated as well as in cilia (+) cells that were stationary. This result was confirmed in cilia knockout adult mice that had lower renal RKIP levels compared with adult mice with cilia. Downstream of RKIP, expression of phosphorylated ERK was decreased only in cells that had cilia and were subjected to constant cilia bending. Furthermore, elevated RKIP levels were associated with reduced cell proliferation. Blockade of PKC abrogated ciliary bending-induced increases in RKIP. In summary, we found that ciliary movement may help control the expression of the Raf-1 kinase inhibitor protein and thus maintain cell differentiation. In terms of polycystic kidney disease, loss of cilia and therefore sensitivity to flow may lead to reduced RKIP levels, activation of the MAPK pathway, and contribute to the formation of cysts.
  • Authors

    Published In

    Keywords

  • Analysis of Variance, Animals, Cell Differentiation, Cell Line, Cell Proliferation, Cilia, Epithelial Cells, Extracellular Signal-Regulated MAP Kinases, Kidney Tubules, Collecting, Mechanotransduction, Cellular, Mice, Mice, Knockout, Mice, Transgenic, Phosphatidylethanolamine Binding Protein, Phosphorylation, Protein Kinase C, Protein Kinase Inhibitors, Proteomics, Rotation, Time Factors, Tumor Suppressor Proteins
  • Digital Object Identifier (doi)

    Authorlist

  • Sas KM; Janech MG; Favre E; Arthur JM; Bell PD
  • Start Page

  • F1163
  • End Page

  • F1170
  • Volume

  • 300
  • Issue

  • 5