The human TRPV6 channel protein is associated with cyclophilin B in human placenta.
Transcellular calcium transport in the kidney, pancreas, small intestine, and placenta is partly mediated by transient receptor potential (TRP) channels. The highly selective TRPV6 calcium channel protein is most likely important for the calcium transfer in different specialized epithelial cells. In the human placenta the protein is expressed in trophoblast tissue, where it is implicated in the transepithelial calcium transfer from mother to the fetus. We enriched the TRPV6 channel protein endogenously expressed in placenta together with annexin A2 and cyclophilin B (CypB), which is a member of the huge immunophilin family. In the human placenta TRPV6 and CypB are mainly located intracellularly in the syncytiotrophoblast layer, but a small amount of the mature glycosylated TRPV6 channel protein and CypB is also expressed in microvilli apical membranes, the fetomaternal barrier. To understand the role of CypB on the TRPV6 channel function, we evaluated the effect of CypB co-expression on TRPV6-mediated calcium uptake into Xenopus laevis oocytes expressing TRPV6. A significant increase of TRPV6-mediated calcium uptake was observed after CypB/TRPV6 co-expression. This stimulatory effect of CypB was reversed by the immunosuppressive drug cyclosporin A, which inhibits the enzymatic activity of CypB. Cyclosporin A had no significant effect on TRPV6 and CypB protein expression levels in the oocytes. In summary, our results establish CypB as a new TRPV6 accessory protein with potential involvement in TRPV6 channel activation through its peptidyl-prolyl cis/trans isomerase activity.
Stumpf
Tobias
T
Abteilungen Proteinfunktion/Proteomics and Allgemeine Zoologie des Fachbereichs Biologie, Technische Universität Kaiserslautern, Kaiserslautern, Germany.
Zhang
Qi
Q
Hirnet
Daniela
D
Lewandrowski
Urs
U
Sickmann
Albert
A
Wissenbach
Ulrich
U
Dörr
Janka
J
Lohr
Christian
C
Deitmer
Joachim W
JW
Fecher-Trost
Claudia
C
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D021983:Cyclophilins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000378:metabolism*; D014982:Xenopus laevis
D015220:Calcium Channels; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human; C081786:cyclophilin B; D021983:Cyclophilins