title: Rab11b and its effector Rip11 regulate the acidosis-induced traffic of V-ATPase in salivary ducts.
abstract: 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.
authors: Department of Molecular Embryology, Institute for Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany.
authors: Oliver
authors: O
authors: Oehlke
authors: Henno W
authors: HW
authors: Martin
authors: Nadja
authors: N
authors: Osterberg
authors: Eleni
authors: E
authors: Roussa
mesh_terms: D000138:Acidosis / Q000201:enzymology* / Q000473:pathology; D000143:Acids / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D005110:Extracellular Space / Q000201:enzymology; D055785:Gene Knockdown Techniques; D006801:Humans; D042541:Intracellular Space / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D018987:Salivary Ducts / Q000201:enzymology* / Q000473:pathology*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000143:Acids; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; D025262:Vacuolar Proton-Translocating ATPases; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C485422:RAB11FIP5 protein, human