Ciliary calcium signaling is modulated by kidney injury molecule-1 (Kim1)

  • Fruzsina Kotsis
  • Roland Nitschke
  • Christopher Boehlke
  • Mikhail Bashkurov
  • Gerd Walz
  • E. Wolfgang KuehnEmail author
Cell and Molecular Physiology


Primary cilia have been shown to play an important role in embryonic development as well as in postnatal life. Dysfunctional cilia are associated with situs inversus, retinal abnormalities, impaired mucociliary clearance, infertility, hydrocephalus, and congenital renal cysts. In autosomal dominant polycystic kidney disease, mutations of the ciliary proteins polycystin1 or the transient receptor potential (TRP) channel family protein polycystin2 (TRPP2) cause progressive cyst formation and destruction of the kidney. Primary cilia act as flow sensors and respond to flow-mediated bending with a prolonged intracellular calcium increase, which appears to require an intact polycystin protein complex. We have established a novel flow chamber system, which allows us to study renal epithelial cells by live cell imaging. We show that MDCK cells respond to flow by a delayed increase in intracellular calcium and that this response requires these cells to be ciliated. We show that a novel interactor of TRPP2, kidney injury molecule-1 (Kim1), which is expressed at low levels in the normal kidney and upregulated after ischemia, in renal cell cancer and in PKD is targeted to primary cilia when stably expressed in MDCK cells. We demonstrate that expression of tyrosine mutant Kim1, lacking a conserved tyrosine in the intracellular tail, abolishes the calcium increase in response to flow in a dominant negative manner. These results establish Kim1 as a novel regulatory molecule of flow-induced calcium signaling.


Cilium Flow Calcium ADPKD Cystic disease Kim1 Tim-1 HAVcr 



autosomal dominant polycystic kidney disease






transient receptor potential


intraflagellar transport


kidney injury molecule-1


T-cell immunoglobulin mucin


T helper type 2


hepatitis A virus cellular receptor


yellow fluorescent protein


Madin Darby canine kidney



We thank Simone Braeg for the expert technical assistance. We are grateful to Michael Kottgen for critically appraising the manuscript and to the members of the Renal Unit for the helpful discussions. This work was funded by DFG WA597 (GW).

Supplementary material

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Fruzsina Kotsis
    • 1
  • Roland Nitschke
    • 2
  • Christopher Boehlke
    • 1
  • Mikhail Bashkurov
    • 1
  • Gerd Walz
    • 1
  • E. Wolfgang Kuehn
    • 1
    Email author
  1. 1.Department of MedicineUniversity Hospital FreiburgFreiburgGermany
  2. 2.Department of Developmental BiologyFreiburg UniversityFreiburgGermany

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