Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes.
The epithelial Ca2+ channel TRPV5 (ECaC1) plays a key role in renal and intestinal Ca2+ (re)absorption and is thus regulated by 1,25(OH) 2D3. The present study aims to explore whether TRPV5 is regulated by the serum and glucocorticoid inducible kinase SGK1, a kinase transcriptionally upregulated by 1,25(OH) 2D3. To this end cRNA encoding TRPV5 has been injected into Xenopus oocytes with or without additional injection of SGK1, its isoforms SGK2 and SGK3, constitutively active (S422D)SGK1, inactive (K127N)SGK1, constitutively active (T308D,S473D)PKB and/or the Na+/H+ exchanger regulating factor NHERF2. In Xenopus laevisoocytes expression of TRPV5 increases uptake of tracer Ca(S422D;) and induces a Ca2+ current (ICa). In the presence of Cl-, TRPV5 mediated Ca2+ entry leads to secondary activation of Ca(2+)-sensitive Cl- channels (ICl(Ca)). Coexpression of TRPV5 with both (S422D)SGK1 and NHERF2 stimulates tracer Ca2+ entry, ICa and ICl(Ca). The effect of (S422D)SGK1 on TRPV5 and NHERF2 expressing oocytes is mimicked by SGK1 and SGK3, but not by SGK2, constitutively active (T308D,S473D)PKB or inactive (K127N)SGK1. The observations suggest that SGK1, SGK3 and NHERF2 regulate TRPV5 and are thus likely to participate in the regulation of calcium homeostasis.
Dept. of Physiology I, University of Tübingen, Germany.
Hamdy M
HM
Embark
Iwan
I
Setiawan
Susanne
S
Poppendieck
Stan F J
SF
van de Graaf
Christoph
C
Boehmer
Monica
M
Palmada
Thomas
T
Wieder
Ruediger
R
Gerstberger
Philip
P
Cohen
C Chris
CC
Yun
René J M
RJ
Bindels
Florian
F
Lang
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004553:Electric Conductivity; D006801:Humans; D017874:Immediate-Early Proteins; D017136:Ion Transport / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009865:Oocytes / Q000502:physiology; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011817:Rabbits; D012430:Ruthenium Red / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers; D050916:TRPV Cation Channels; D014981:Xenopus; D000099184:Serum-Glucocorticoid Regulated Kinases
D002118:Calcium; D015220:Calcium Channels; D003598:Cytoskeletal Proteins; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D012430:Ruthenium Red; D017923:Sodium-Hydrogen Exchangers; D050916:TRPV Cation Channels; D000099184:Serum-Glucocorticoid Regulated Kinases; C492239:TRPV5 protein, human; C093376:sodium-hydrogen exchanger regulatory factor