Inhibition of taurine transport by cyclosporin A is due to altered surface abundance of the taurine transporter and is reversible.
We have investigated the underlying mechanism of the CsA-induced inhibition of taurine transport using a cell line permanently expressing the mouse taurine transporter (mTauT) tagged with the green-fluorescence protein (GFP). CsA inhibited the uptake activity of the expressed mTauT.GFP fusion protein in both dose and time dependent manner. Surface biotinylation assay revealed that the CsA-treatment reduced the relative surface abundance of the taurine transporter without affecting its total expression level. CsA treatment reduced both the taurine uptake and the relative surface abundance of the transporter by similar magnitudes. Conversely, when the CsA was washed off, both the uptake and the relative surface abundance of the transporter recovered fully to the control level. Remarkably, the recovery process was insensitive to the protein synthesis inhibitor cycloheximide. These results suggested that the CsA inhibited taurine transport by altering the surface abundance, possibly by internalization of the expressed taurine transporters.
Tran
Thanh T
TT
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
Qian
Xiaojun
X
Edwards
Cynthia
C
Sarkar
Hemanta K
HK
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D013654:Taurine / Q000378:metabolism*; D000099247:Taurine Transporters
D016572:Cyclosporine; D049452:Green Fluorescent Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D000099247:Taurine Transporters