Redistribution of
acid-base transporters is a crucial regulatory mechanism for many types of cells to cope with extracellular pH changes. In epithelial cells, however, translocation of
acid-base transporters ultimately leads to changes in vectorial transport of H+ and HCO3-. We have previously shown that the
bicarbonate-secreting epithelium of salivary ducts responds to changes of systemic acid-base balance by adaptive redistribution of H+ and HCO3- transporters, thereby influencing the ionic composition and buffering capacity of saliva. However, the specific
proteins involved in regulated vesicular traffic of
acid-base transporters are largely unknown. In the present study we have investigated the impact of Rab11 family members on the
acidosis-induced trafficking of the vacuolar-type
H+-ATPase (V-
ATPase) in salivary duct cells in vitro using the human submandibular cell line of ductal origin HSG as an experimental model. The results show that Rab11b is expressed in salivary ducts and exhibits a significantly higher co-localization with V-
ATPase than Rab11a and Rab25. We also show that Rab11 but not Rab25 interacts with the ε subunit of V-
ATPase. Extracellular
acidosis up-regulates Rab11b expression and
protein abundance in HSG cells and causes translocation of the V-
ATPase from intracellular pools toward the plasma membrane. Loss-of-function experiments using specific
siRNA either against Rab11b or against its effector Rip11 prevent
acidosis-induced V-
ATPase translocation. These data introduce Rab11b as a crucial regulator and Rip11 as mediator of
acidosis-induced V-
ATPase traffic in duct cells of submandibular gland.