A family of Rab GTPases has been implicated in the regulation of intracellular vesicular traffic with specialized transport functions of the different Rab proteins in the secretory and endocytic pathways [5]. Rab11a is well-established as a participant in the regulation of recycling endosomal trafficking. Rab11a is associated with vesicles in the apical portion of epithelial
XAV939 near the centrosome and beneath the apical plasma membrane. Rab3 is involved in Ca2+-dependent exocytosis [30]. Rab5 is present on early endosomes and regulate early steps of the endocytic process [14], [19] and [31]. Arf-1 belongs to the Sar1/Arf family of small G proteins and is important in the regulation of
exocytosis [32]. Our results demonstrate an important role for both Rab11a and Rab3a in upregulation of ENaC activity. In contrast, neither Rab5 nor Rab27a or Arf-1, were found to regulate ENaC activity. The current results demonstrate for the first time that Rab11a small GTPases are important in the trafficking of ENaC. Together, these results identify an important new pathway regulating ENaC channel density necessary for the maintenance of proper cell homeostasis.
