TRPP2 and TRPV4 form a polymodal sensory channel complex

Michael Köttgen, Björn Buchholz, Miguel A. Garcia-Gonzalez, Fruzsina Kotsis, Xiao Fu, Mara Doerken, Christopher Boehlke, Daniel Steffl, Robert Tauber, Tomasz Wegierski, Roland Nitschke, Makoto Suzuki, Albrecht Kramer-Zucker, Gregory G. Germino, Terry Watnick, Jean Prenen, Bernd Nilius, E. Wolfgang Kuehn, Gerd Walz

Research output: Contribution to journalArticle

Abstract

The primary cilium has evolved as a multifunctional cellular compartment that decorates most vertebrate cells. Cilia sense mechanical stimuli in various organs, but the molecular mechanisms that convert the deflection of cilia into intracellular calcium transients have remained elusive. Polycystin-2 (TRPP2), an ion channel mutated in polycystic kidney disease, is required for cilia-mediated calcium transients but lacks mechanosensitive properties. We find here that TRPP2 utilizes TRPV4 to form a mechano- and thermosensitive molecular sensor in the cilium. Depletion of TRPV4 in renal epithelial cells abolishes flow-induced calcium transients, demonstrating that TRPV4, like TRPP2, is an essential component of the ciliary mechanosensor. Because TRPV4-deficient zebrafish and mice lack renal cysts, our findings challenge the concept that defective ciliary flow sensing constitutes the fundamental mechanism of cystogenesis.

Original languageEnglish (US)
Pages (from-to)437-447
Number of pages11
JournalJournal of Cell Biology
Volume182
Issue number3
DOIs
StatePublished - Aug 11 2008

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Köttgen, M., Buchholz, B., Garcia-Gonzalez, M. A., Kotsis, F., Fu, X., Doerken, M., Boehlke, C., Steffl, D., Tauber, R., Wegierski, T., Nitschke, R., Suzuki, M., Kramer-Zucker, A., Germino, G. G., Watnick, T., Prenen, J., Nilius, B., Kuehn, E. W., & Walz, G. (2008). TRPP2 and TRPV4 form a polymodal sensory channel complex. Journal of Cell Biology, 182(3), 437-447. https://doi.org/10.1083/jcb.200805124