RGS2 inhibits the epithelial Ca2+ channel TRPV6.
Publication year
2006Source
Journal of Biological Chemistry, 281, 40, (2006), pp. 29669-74ISSN
Publication type
Article / Letter to editor
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Organization
Physiology
Periodontology and Biomaterials
Cell Physiology
Journal title
Journal of Biological Chemistry
Volume
vol. 281
Issue
iss. 40
Page start
p. 29669
Page end
p. 74
Subject
IGMD 9: Renal disorder; NCMLS 5: Membrane transport and intracellular motility; UMCN 5.4: Renal disordersAbstract
The epithelial Ca(2+) channels TRPV5 and TRPV6 constitute the apical Ca(2+) entry pathway in the process of active Ca(2+) (re)absorption. By yeast two-hybrid and glutathione S-transferase pulldown analysis we identified RGS2 as a novel TRPV6-associated protein. RGS proteins determine the inactivation kinetics of heterotrimeric G-protein-coupled receptor (GPCR) signaling by regulating the GTPase activity of G(alpha) subunits. Here we demonstrate that TRPV6 interacts with the NH(2)-terminal domain of RGS2 in a Ca(2+)-independent fashion and that overexpression of RGS2 reduces the Na(+) and Ca(2+) current of TRPV6 but not that of TRPV5-transfected human embryonic kidney 293 (HEK293) cells. In contrast, overexpression of the deletion mutant DeltaN-RGS2, lacking the NH(2)-terminal domain of RGS2, in TRPV6-expressing HEK293 cells did not show this inhibition. Furthermore, cell surface biotinylation indicated that the inhibitory effect of RGS2 on TRPV6 activity is not mediated by differences in trafficking or retrieval of TRPV6 from the plasma membrane. This effect probably results from the direct interaction between RGS2 and TRPV6, affecting the gating properties of the channel. Finally, the scaffolding protein spinophilin, shown to recruit RGS2 and regulate GPCR-signaling via G(alpha), did not affect RGS2 binding and electrophysiological properties of TRPV6, indicating a GPCR-independent mechanism of TRPV6 regulation by RGS2.
This item appears in the following Collection(s)
- Academic publications [238430]
- Electronic publications [122512]
- Faculty of Medical Sciences [90359]
- Open Access publications [97507]
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