title: Rab11b regulates the trafficking and recycling of the epithelial sodium channel (ENaC).
abstract: Expression of the epithelial sodium channel (ENaC) at the apical membrane of cortical collecting duct (CCD) principal cells is modulated by regulated trafficking mediated by vesicle insertion and retrieval. Small GTPases are known to facilitate vesicle trafficking, recycling, and membrane fusion events; however, little is known about the specific Rab family members that modify ENaC surface density. Using a mouse CCD cell line that endogenously expresses ENaC (mpkCCD), the channel was localized to both Rab11a- and Rab11b-positive endosomes by immunoisolation and confocal fluorescent microscopy. Expression of a dominant negative (DN) form of Rab11a or Rab11b significantly reduced the basal and cAMP-stimulated ENaC-dependent sodium (Na(+)) transport. The greatest reduction in Na(+) transport was observed with the expression of DN-Rab11b. Furthermore, small interfering RNA-mediated knockdown of each Rab11 isoform demonstrated the requirement for Rab11b in ENaC surface expression. These data indicate that Rab11b, and to a lesser extent Rab11a, is involved in establishing the constitutive and cAMP-stimulated Na(+) transport in mpkCCD cells.
authors: Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15261, USA. michael7@pitt.edu
authors: Michael B
authors: MB
authors: Butterworth
authors: Robert S
authors: RS
authors: Edinger
authors: Mark R
authors: MR
authors: Silvis
authors: Luciana I
authors: LI
authors: Gallo
authors: Xiubin
authors: X
authors: Liang
authors: Gerard
authors: G
authors: Apodaca
authors: Raymond A
authors: RA
authors: Frizzell
authors: Raymond A
authors: RA
authors: Fizzell
authors: John P
authors: JP
authors: Johnson
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D053503:Epithelial Sodium Channels; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins