Inorganic Polyphosphate Modulates TRPM8 Channels

被引:105
作者
Zakharian, Eleonora
Thyagarajan, Baskaran
French, Robert J.
Pavlov, Evgeny
Rohacs, Tibor
机构
[1] Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ
[2] Department of Physiology and Biophysics, University of Calgary, Calgary, AB
来源
PLOS ONE | 2009年 / 4卷 / 04期
关键词
D O I
10.1371/journal.pone.0005404
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Polyphosphate (polyP) is an inorganic polymer built of tens to hundreds of phosphates, linked by high-energy phosphoanhydride bonds. PolyP forms complexes and modulates activities of many proteins including ion channels. Here we investigated the role of polyP in the function of the transient receptor potential melastatin 8 (TRPM8) channel. Using whole-cell patch-clamp and fluorescent calcium measurements we demonstrate that enzymatic breakdown of polyP by exopolyphosphatase (scPPX1) inhibits channel activity in human embryonic kidney and F-11 neuronal cells expressing TRPM8. We demonstrate that the TRPM8 channel protein is associated with polyP. Furthermore, addition of scPPX1 altered the voltage-dependence and blocked the activity of the purified TRPM8 channels reconstituted into planar lipid bilayers, where the activity of the channel was initiated by cold and menthol in the presence of phosphatidylinositol 4,5-biphosphate (PtdIns(4,5) P-2). The biochemical analysis of the TRPM8 protein also uncovered the presence of poly-(R)-3-hydroxybutyrate (PHB), which is frequently associated with polyP. We conclude that the TRPM8 protein forms a stable complex with polyP and its presence is essential for normal channel activity.
引用
收藏
页数:12
相关论文
共 53 条
[41]   PIP2 is a necessary cofactor for ion channel function:: How and why? [J].
Suh, Byung-Chang ;
Hille, Bertil .
ANNUAL REVIEW OF BIOPHYSICS, 2008, 37 :175-195
[42]  
TAMMENKOSKI M, 2007, KINETIC MUTATIONAL A, P9302
[43]   Human metastasis regulator protein H-prune is a short-chain exopolyphosphatase [J].
Tammenkoski, Marko ;
Koivula, Katja ;
Cusanelli, Emilio ;
Zollo, Massimo ;
Steegborn, Clemens ;
Baykov, Alexander A. ;
Lahti, Reijo .
BIOCHEMISTRY, 2008, 47 (36) :9707-9713
[44]   Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells [J].
Thebault, S ;
Lemonnier, L ;
Bidaux, G ;
Flourakis, M ;
Bavencoffe, A ;
Gordienko, D ;
Roudbaraki, M ;
Delcourt, P ;
Panchin, Y ;
Shuba, Y ;
Skryma, R ;
Prevarskaya, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (47) :39423-39435
[45]   The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels [J].
Voets, T ;
Droogmans, G ;
Wissenbach, U ;
Janssens, A ;
Flockerzi, V ;
Nilius, B .
NATURE, 2004, 430 (7001) :748-754
[46]   Modulation of TRPs by PIPs [J].
Voets, Thomas ;
Nilius, Bernd .
JOURNAL OF PHYSIOLOGY-LONDON, 2007, 582 (03) :939-944
[47]   TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli [J].
Voets, Thomas ;
Owsianik, Grzegorz ;
Janssens, Annelies ;
Talavera, Karel ;
Nilius, Bernd .
NATURE CHEMICAL BIOLOGY, 2007, 3 (03) :174-182
[48]   Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells [J].
Wang, LH ;
Fraley, CD ;
Faridi, J ;
Kornberg, A ;
Roth, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (20) :11249-11254
[49]  
WURST H, 1994, J BIOL CHEM, V269, P10996
[50]   Sorting signal of Escherichia coli OmpA is modified by oligo-(R)-3-hydroxybutyrate [J].
Xian, Mo ;
Fuerst, Michelle M. ;
Shabalin, Yuri ;
Reusch, Rosetta N. .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2007, 1768 (11) :2660-2666