Mol Cell Biol. 2006 Jan;26(1):303-12.

Direct interaction with Rab11a targets the epithelial Ca2+ channels TRPV5 and TRPV6 to the plasma membrane.External

van de Graaf, S. F., Chang, Q., Mensenkamp, A. R., Hoenderop, J. G., Bindels, R. J.,
["Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands."]
TRPV5 and TRPV6 are the most Ca2+-selective members of the transient receptor potential (TRP) family of cation channels and play a pivotal role in the maintenance of Ca2+ balance in the body. However, little is known about the mechanisms controlling the plasma membrane abundance of these channels to regulate epithelial Ca2+ transport. In this study, we demonstrated the direct and specific interaction of GDP-bound Rab11a with TRPV5 and TRPV6. Rab11a colocalized with TRPV5 and TRPV6 in vesicular structures underlying the apical plasma membrane of Ca2+-transporting epithelial cells. This GTPase recognized a conserved stretch in the carboxyl terminus of TRPV5 that is essential for channel trafficking. Furthermore, coexpression of GDP-locked Rab11a with TRPV5 or TRPV6 resulted in significantly decreased Ca2+ uptake, caused by diminished channel cell surface expression. Together, our data demonstrated the important role of Rab11a in the trafficking of TRPV5 and TRPV6. Rab11a exerts this function in a novel fashion, since it operates via direct cargo interaction while in the GDP-bound configuration.
PMID: 16354700External
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Screening Toggle
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPV5 Link Rab11a Inference Prediction 16354700
TRPV6 Link Rab11a Yeast two-hybrid Mouse C-terminus Mouse Kidney cDNA library 16354700
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Validation: In vitro validation Toggle
  Assay with recombinant proteins Reference
TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Expression system Species Region Expression system
TRPV5 Link Rab11a Fusion protein-pull down assay Mouse Full-length E. coli Mouse Full-length In vitro translation 16354700
TRPV6 Link Rab11a Fusion protein-pull down assay Mouse Full-length E. coli Mouse Full-length In vitro translation 16354700
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Validation: In vivo validation Toggle
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPV5 Link Rab11a Co-immunoprecipitation Xenopus oocyte Mouse Full-length Mouse Full-length 16354700
TRPV5 Link Rab11a Co-immunofluorescence staining Xenopus oocyte Mouse Full-length Mouse Full-length 16354700
TRPV5 Link Rab11a Co-immunofluorescence staining Mouse kidney section 16354700
TRPV6 Link Rab11a Co-immunofluorescence staining Mouse kidney section 16354700
TRPV6 Link Rab11a Co-immunofluorescence staining Xenopus oocyte Mouse Full-length Mouse Full-length 16354700
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Characterization Toggle
  Binding region mapping Stoichiometry Affinity (Kd) Reference
TRP channel Interactor
TRP channel Interactor Method Species Region Species Region
TRPV5 Link Rab11a Fusion protein-pull down assay Mouse 596-600 Mouse Not determined 16354700
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Functional consequence Toggle
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPV5 Link Rab11a Co-immunofluorescence staining Increase in plasma membrane level 16354700
TRPV5 Link Rab11a Calcium measurement Activation 16354700
TRPV6 Link Rab11a Co-immunofluorescence staining Increase in plasma membrane level 16354700
TRPV6 Link Rab11a Calcium measurement Activation 16354700
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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