The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel.
Blood calcium concentration is maintained within a narrow range despite large variations in dietary input and body demand. The Transient Receptor Potential ion channel TRPV5 has been implicated in this process. We report here that TRPV5 is stimulated by the mammalian hormone klotho. Klotho, a beta-glucuronidase, hydrolyzes extracellular sugar residues on TRPV5, entrapping the channel in the plasma membrane. This maintains durable calcium channel activity and membrane calcium permeability in kidney. Thus, klotho activates a cell surface channel by hydrolysis of its extracellular N-linked oligosaccharides.
Chang
Q
Q
Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands.
Hoefs
S
S
van der Kemp
A W
AW
Topala
C N
CN
Bindels
R J
RJ
Hoenderop
J G
JG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D000090265:Klotho Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018408:Patch-Clamp Techniques; D021381:Protein Transport; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D015220:Calcium Channels; D008565:Membrane Proteins; D050916:TRPV Cation Channels; C120776:TRPV6 channel; C492240:Trpv5 protein, mouse; D012964:Sodium; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium