Expression of the ammonia transporter, rh C glycoprotein, in normal and neoplastic human kidney.
Recent studies have identified the presence of a novel Mep/Amt/Rh glycoprotein family of proteins that may play an important role in transmembrane ammonia transport. One of the mammalian members of this family, Rh C glycoprotein (RhCG), transports ammonia, is expressed in distal nephron sites that are critically important for ammonia secretion, exhibits increased expression in response to chronic metabolic acidosis, and originally was cloned as a tumor-related protein. The purpose of our studies was to determine the localization of RhCG in the normal and neoplastic human kidney. Immunoblot analysis of human renal cortical protein lysates demonstrated RhCG protein expression with a molecular weight of approximately 52 kD. Immunohistochemistry revealed both apical and basolateral Rhcg expression in the distal convoluted tubule, connecting segment, and initial collecting tubule and throughout the collecting duct. Co-localization with calbindin-D28k, H(+)-ATPase, aquaporin-2, and pendrin showed that distal convoluted tubule and connecting segment cells, A-type intercalated cells, and non-A, non-B cells express RhCG and that B-type intercalated cells, principal cells, and inner medullary collecting duct cells do not. In renal neoplasms, RhCG was expressed by chromophobe renal cell carcinoma and renal oncocytoma but not by clear cell renal cell carcinoma or by papillary renal cell carcinomas. These studies suggest that RhCG contributes to both apical and basolateral membrane ammonia transport in the human kidney. Furthermore, renal chromophobe renal cell carcinoma and renal oncocytoma seem to originate from the A-type intercalated cell.
Han
Ki-Hwan
KH
Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, P.O. Box 100224, Gainesville, FL 32610-0224, USA.
Croker
Byron P
BP
Clapp
William L
WL
Werner
Dietrich
D
Sahni
Manisha
M
Kim
Jin
J
Kim
Hye-Young
HY
Handlogten
Mary E
ME
Weiner
I David
ID
D018263:Adenocarcinoma, Follicular / Q000378:metabolism / Q000473:pathology; D018249:Adenoma, Oxyphilic / Q000378:metabolism / Q000473:pathology; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D064092:Calbindin 1; D064026:Calbindins; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D027682:Cation Transport Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D006180:Proton-Translocating ATPases / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D000076988:Sulfate Transporters
C496023:AQP2 protein, human; D051399:Aquaporin 2; C576498:CALB1 protein, human; C576499:Calb1 protein, mouse; D064092:Calbindin 1; D064026:Calbindins; D027682:Cation Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C413213:RHCG protein, human; D064030:S100 Calcium Binding Protein G; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000641:Ammonia; D006180:Proton-Translocating ATPases