WNK4 regulates the secretory pathway via which TRPV5 is targeted to the plasma membrane.
TRPV5 and TRPV6 are two closely related epithelial calcium channels that mediate apical calcium entry in the transcellular calcium transport pathway. TRPV5, but not TRPV6, is enhanced by protein kinase WNK4 when expressed in Xenopus laevis oocytes. We report that the majority of human TRPV5 exogenously expressed in the Xenopus oocyte plasma membrane was complexly N-glycosylated whereas that for human TRPV6 was core-glycosylated. Unglycosylated N358Q mutants of TRPV5 and TRPV6 were able to be expressed in the plasma membrane albeit with decreased abilities in mediating calcium uptake. Syntaxin 6, a SNARE protein in the trans-Golgi network, blocked the complex glycosylation of TRPV5 and TRPV6, rendered the channels in core-glycosylated form. Blocking complex glycosylation of TRPV5 either by syntaxin 6 or by N358Q mutation abolished the enhancing effect of WNK4 on TRPV5. Thus the difference in membrane expression of TRPV5 and TRPV6 explains the selective effect of WNK4 on TRPV5, which is likely on the secretory pathway involving complex glycosylation of channel proteins.
Jiang
Yi
Y
Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, AL 35294-0006, USA.
Cong
Peilong
P
Williams
Shawn R
SR
Zhang
Wei
W
Na
Tao
T
Ma
He-Ping
HP
Peng
Ji-Bin
JB
D019943:Amino Acid Substitution; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D009154:Mutation; D009865:Oocytes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D001798:Blood Proteins; D015220:Calcium Channels; D050765:Qa-SNARE Proteins; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; C422827:TRPV6 protein, human; D017346:Protein Serine-Threonine Kinases; C433806:WNK4 protein, human