Rab11b regulates the trafficking and recycling of the epithelial sodium channel (ENaC)

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 eve...

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Bibliographic Details
Published in:American journal of physiology. Renal physiology 2012-03, Vol.302 (5), p.F581-F590
Main Authors: Butterworth, Michael B, Edinger, Robert S, Silvis, Mark R, Gallo, Luciana I, Liang, Xiubin, Apodaca, Gerard, Frizzell, Raymond A, Fizzell, Raymond A, Johnson, John P
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cells
Cells, Cultured
Endosomes - metabolism
Epithelial Cells - cytology
Epithelial Cells - metabolism
Epithelial Sodium Channels - metabolism
Gene expression
Kidney Tubules, Collecting - cytology
Kidney Tubules, Collecting - metabolism
Membranes
Mice
Protein Transport
rab GTP-Binding Proteins - metabolism
Rodents
Sodium
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Summary: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.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00304.2011