title: Direct interaction with Rab11a targets the epithelial Ca2+ channels TRPV5 and TRPV6 to the plasma membrane.
abstract: 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.
authors.affiliation: Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.
authors.forename: Stan F J
authors.initials: SF
authors.lastname: van de Graaf
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.forename: Arjen R
authors.initials: AR
authors.lastname: Mensenkamp
authors.forename: Joost G J
authors.initials: JG
authors.lastname: Hoenderop
authors.forename: René J M
authors.initials: RJ
authors.lastname: Bindels
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D025941:Protein Interaction Mapping; D021381:Protein Transport; D050916:TRPV Cation Channels / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D002118:Calcium; D015220:Calcium Channels; D006153:Guanosine Diphosphate; D050916:TRPV Cation Channels; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C120776:TRPV6 channel; C492240:Trpv5 protein, mouse