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Identification of BSPRY as a novel auxiliary protein inhibiting TRPV5 activity van de Graaf SF; van der Kemp AW; van den Berg D; van Oorschot M; Hoenderop JG; Bindels RJJ Am Soc Nephrol 2006[Jan]; 17 (1): 26-30Transient 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.|Amino Acid Sequence[MESH]|Animals[MESH]|Calcitriol/physiology[MESH]|Calcium Channels/analysis/physiology[MESH]|Calcium/metabolism[MESH]|Cell Line[MESH]|Molecular Sequence Data[MESH]|Proteins/analysis/chemistry/*physiology[MESH]|TRPV Cation Channels/analysis/*antagonists & inhibitors/physiology[MESH]|Xenopus[MESH] |
