Distribution of Rab GTPases in mouse kidney and comparison with vacuolar H+-ATPase.
BACKGROUND
Vacuolar H+-ATPases (V-ATPases) are essential for renal bicarbonate transport in both the proximal and distal nephron. Regulation of proton transport occurs, in part, by vesicle-mediated traffic of V-ATPases between intracellular vacuoles and the plasma membrane. Although the proteins involved in regulated V-ATPase traffic are largely unknown, Rab GTPases have a central role in the traffic and recycling of other membrane proteins.


METHODS
To identify candidate Rab GTPases potentially involved in V-ATPase traffic, immunocytochemical and subcellular fractionation studies were used to evaluate the distribution to sites of abundant V-ATPase of 5 Rab GTPases expressed in kidney, Rab5a, Rab11, Rab13, Rab18, and Rab20.


RESULTS
The immunocytochemical distribution of Rab5a and Rab13 and the subcellular distribution of Rab18 were not compatible with a role in V-ATPase traffic. In contrast, Rab11 colocalized with V-ATPase in apical regions of proximal tubule, and Rab20 colocalized with the enzyme in intercalated cells. Rab11 and Rab20 were enriched in membrane fractions that were also enriched in V-ATPase B2 and B1 subunit isoforms, respectively.


CONCLUSIONS
The immunohistochemical data in combination with the membrane fractionation studies are consistent with a potential role for Rab11 and Rab20 in regulating V-ATPase traffic in specific segments of the nephron.
Curtis
Lisa M
LM
Department of Medicine, University of Florida, Gainesville, Florida, USA. lmcurtis@uab.edu
Gluck
Stephen
S
D000818:Animals; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D014018:Tissue Distribution; D014617:Vacuoles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
D006180:Proton-Translocating ATPases; D020691:rab GTP-Binding Proteins