Phosphatidylinositol phosphate-dependent regulation of Xenopus ENaC by MARCKS protein

被引:54
作者
Alli, Abdel A. [1 ]
Bao, Hui-Fang
Alli, Alia A.
Aldrugh, Yasir
Song, John Z.
Ma, He-Ping
Yu, Ling
Al-Khalili, Otor
Eaton, Douglas C.
机构
[1] Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA
基金
美国国家卫生研究院;
关键词
ENaC; MARCKS; phospholipids; PIP2; PKC; EPITHELIAL SODIUM-CHANNEL; NA+ CHANNEL; KINASE-C; SUBSTRATE MARCKS; FLUID CLEARANCE; PHOSPHORYLATION; ALPHA; EXPRESSION; BINDING; 3,4,5-TRISPHOSPHATE;
D O I
10.1152/ajprenal.00703.2011
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Alli AA, Bao H, Alli AA, Aldrugh Y, Song JZ, Ma H, Yu L, Al-Khalili O, Eaton DC. Phosphatidylinositol phosphate-dependent regulation of Xenopus ENaC by MARCKS protein. Am J Physiol Renal Physiol 303: F800-F811, 2012. First published July 11, 2012; doi:10.1152/ajprenal.00703.2011.-Phosphatidylinositol phosphates (PIPs) are known to regulate epithelial sodium channels (ENaC). Lipid binding assays and coimmunoprecipitation showed that the amino-terminal domain of the beta- and gamma-subunits of Xenopus ENaC can directly bind to phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 3,4,5-trisphosphate (PIP3), and phosphatidic acid (PA). Similar assays demonstrated various PIPs can bind strongly to a native myristoylated alanine-rich C-kinase substrate (MARCKS), but weakly or not at all to a mutant form of MARCKS. Confocal microscopy demonstrated colocalization between MARCKS and PIP2. Confocal microscopy also showed that MARCKS redistributes from the apical membrane to the cytoplasm after PMA-induced MARCKS phosphorylation or ionomycin-induced intracellular calcium increases. Fluorescence resonance energy transfer studies revealed ENaC and MARCKS in close proximity in 2F3 cells when PKC activity and intracellular calcium concentrations are low. Transepithelial current measurements from Xenopus 2F3 cells treated with PMA and single-channel patch-clamp studies of Xenopus 2F3 cells treated with a PKC inhibitor altered Xenopus ENaC activity, which suggest an essential role for MARCKS in the regulation of Xenopus ENaC activity.
引用
收藏
页码:F800 / F811
页数:12
相关论文
共 46 条
[1]   THE MARCKS BROTHERS - A FAMILY OF PROTEIN-KINASE-C SUBSTRATES [J].
ADEREM, A .
CELL, 1992, 71 (05) :713-716
[2]   Identification and characterization of MARCKS in Xenopus laevis [J].
Ali, N ;
Macala, LJ ;
Hayslett, JP .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 234 (01) :143-146
[3]   A ROLE FOR MARCKS, THE ALPHA-ISOZYME OF PROTEIN-KINASE-C AND MYOSIN-I IN ZYMOSAN PHAGOCYTOSIS BY MACROPHAGES [J].
ALLEN, LAH ;
ADEREM, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (03) :829-840
[4]   Molecular Approaches to Examine the Phosphorylation State of the C Type Natriuretic Peptide Receptor [J].
Alli, Abdel A. ;
Gower, William R., Jr. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2010, 110 (04) :985-994
[5]   The C type natriuretic peptide receptor tethers AHNAK1 at the plasma membrane to potentiate arachidonic acid-induced calcium mobilization [J].
Alli, Abdel A. ;
Gower, William R., Jr. .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2009, 297 (05) :C1157-C1167
[6]   Cross-talk unfolded:: MARCKS proteins [J].
Arbuzova, A ;
Schmitz, AAP ;
Vergères, G .
BIOCHEMICAL JOURNAL, 2002, 362 :1-12
[7]   AMILORIDE-SENSITIVE EPITHELIAL NA+ CHANNEL IS MADE OF 3 HOMOLOGOUS SUBUNITS [J].
CANESSA, CM ;
SCHILD, L ;
BUELL, G ;
THORENS, B ;
GAUTSCHI, I ;
HORISBERGER, JD ;
ROSSIER, BC .
NATURE, 1994, 367 (6462) :463-467
[8]   EXPRESSION CLONING OF THE EPITHELIAL SODIUM-CHANNEL [J].
CANESSA, CM ;
HORISBERGER, JD ;
SCHILD, L ;
ROSSIER, BC .
KIDNEY INTERNATIONAL, 1995, 48 (04) :950-955
[9]   MEMBRANE TOPOLOGY OF THE EPITHELIAL SODIUM-CHANNEL IN INTACT-CELLS [J].
CANESSA, CM ;
MERILLAT, AM ;
ROSSIER, BC .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1994, 267 (06) :C1682-C1690
[10]  
COFFEY ET, 1994, J NEUROCHEM, V63, P1303