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J Cell Biol. 2008 Aug 11;182(3):437-47. doi: 10.1083/jcb.200805124.

TRPP2 and TRPV4 form a polymodal sensory channel complex.

Author information

1
Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany.

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.

PMID:
18695040
PMCID:
PMC2500130
DOI:
10.1083/jcb.200805124
[Indexed for MEDLINE]
Free PMC Article

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