Identification of BSPRY as a novel auxiliary protein inhibiting TRPV5 activity.
Transient receptor potential vallinoid 5 (TRPV5) and TRPV6 are the most Ca2+-selective members of the TRP superfamily and are essential for active Ca2+ (re)absorption in epithelia. However, little is known about intracellular proteins that regulate the activity of these channels. This study identified BSPRY (B-box and SPRY-domain containing protein) as a novel factor involved in the control of TRPV5. The interaction between BSPRY and TRPV5 by GST pull-down and co-immunoprecipitation assays was demonstrated. BSPRY showed co-localization with TRPV5 in mouse kidney. Expression of BSPRY resulted in a significant reduction of the Ca2+ influx in Madin-Darby Canine Kidney cells that stably express TRPV5 without affecting channel cell-surface abundance. Finally, BSPRY expression in kidney was increased in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice, suggesting an inverse regulation by vitamin D3. Together, these results demonstrate the physiologic role of the novel protein BSPRY in the regulation of epithelial Ca2+ transport via negative modulation of TRPV5 activity.
van de Graaf
Stan F J
SF
Cell Physiology, Radboud University Nijmegen Medical Centre, PO Box 9101, NL-6500 HB Nijmegen, The Netherlands.
van der Kemp
Annemiete W C M
AW
van den Berg
Dennis
D
van Oorschot
Mijke
M
Hoenderop
Joost G J
JG
Bindels
René J M
RJ
D000595:Amino Acid Sequence; D000818:Animals; D002117:Calcitriol / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000032:analysis / Q000502:physiology; D002460:Cell Line; D008969:Molecular Sequence Data; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D050916:TRPV Cation Channels / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000502:physiology; D014981:Xenopus
C416225:BSPRY protein, human; D015220:Calcium Channels; D011506:Proteins; D050916:TRPV Cation Channels; C492240:Trpv5 protein, mouse; D002117:Calcitriol; D002118:Calcium