TRPP2 and TRPV4 form a polymodal sensory channel complex

被引：303

作者：

Koetttgen, Michael ^{[1
]}

Buchholz, Bjoern ^{[1
]}

Garcia-Gonzalez, Miguel A. ^{[3
]}

Kotsis, Fruzsina ^{[1
]}

Fu, Xiao ^{[1
]}

Doerken, Mara ^{[1
]}

Boehlke, Christopher ^{[1
]}

Steffl, Daniel ^{[1
]}

Tauber, Robert ^{[1
]}

Wegierski, Tomasz ^{[1
]}

Nitschke, Roland ^{[5
]}

Suzuki, Makoto ^{[2
]}

Kramer-Zucker, Albrecht ^{[1
]}

Germino, Gregory G. ^{[3
]}

Watnick, Terry ^{[3
]}

Prenen, Jean ^{[4
]}

Nilius, Bernd ^{[4
]}

Kuehn, E. Wolfgang ^{[1
]}

Walz, Gerd ^{[1
]}

机构：

[1] Univ Hosp, Div Renal, D-79106 Freiburg, Germany

[2] Jichi Med Sch, Dept Pharmacol, Mimamikawachi, Tochigi 3290498, Japan

[3] Johns Hopkins Univ, Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21205 USA

[4] Katholieke Univ Leuven, Physiol Lab, B-3000 Louvain, Belgium

[5] Univ Freiburg, Dept Dev Biol, D-79104 Freiburg, Germany

来源：

JOURNAL OF CELL BIOLOGY | 2008年 / 182卷 / 03期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1083/jcb.200805124

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 ciliamediated 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.

引用

页码：437 / 447

页数：11

共 46 条

[1]

Arnould T, 1999, MOL CELL BIOL, V19, P3423

[2] PACSINs bind to the TRPV4 cation channel - PACSIN 3 modulates the subcellular localization of TRPV4 [J].