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Molecular and Cellular Biology, January 2006, p. 303-312, Vol. 26, No. 1
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.1.303-312.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Direct Interaction with Rab11a Targets the Epithelial Ca2+ Channels TRPV5 and TRPV6 to the Plasma Membrane

Stan F. J. van de Graaf, Qing Chang, Arjen R. Mensenkamp, Joost G. J. Hoenderop, and René J. M. Bindels*

Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Received 16 June 2005/ Returned for modification 18 July 2005/ Accepted 3 October 2005

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.

* Corresponding author. Mailing address: 286 Cell Physiology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, NL-6500 HB Nijmegen, The Netherlands. Phone: 31-24-3614211. Fax: 31-24-3616413. E-mail: r.bindels{at}ncmls.ru.nl.

Molecular and Cellular Biology, January 2006, p. 303-312, Vol. 26, No. 1
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.1.303-312.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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