Expression of renal and intestinal Na/Pi cotransporters in the absence of GABARAP.
We have recently shown that the abundance of the renal sodium (Na)/inorganic phosphate (Pi) cotransporter NaPi-IIa is increased in the absence of the GABA(A) receptor-associated protein (GABARAP). Accordingly, GABARAP-deficient mice have a reduced urinary excretion of Pi. However, their circulating levels of Pi do not differ from wild-type animals, suggesting the presence of a compensatory mechanism responsible for keeping serum Pi values constant. Here, we aimed first to identify the molecular basis of this compensation by analyzing the expression of Na/Pi cotransporters known to be expressed in the kidney and intestine. We found that, in the kidney, the upregulation of NaPi-IIa is not accompanied by changes on the expression of either NaPi-IIc or PiT2, the other cotransporters known to participate in renal Pi reabsorption. In contrast, the intestinal expression of NaPi-IIb is downregulated in mutant animals, suggesting that a reduced intestinal absorption of Pi could contribute to maintain a normophosphatemic status despite the increased renal retention. The second goal of this work was to study whether the alterations on the expression of NaPi-IIa induced by chronic dietary Pi are impaired in the absence of GABARAP. Our data indicate that, in response to high Pi diets, GABARAP-deficient mice downregulate the expression of NaPi-IIa to levels comparable to those seen in wild-type animals. However, in response to low Pi diets, the upregulation of NaPi-IIa is greater in the mutant mice. Thus, both the basal expression and the dietary-induced upregulation of NaPi-IIa are increased in the absence of GABARAP.
Reining
Sonja C
SC
Institute of Physiology, University of Zurich, Winterthurerstr. 190, 8057, Zurich, Switzerland.
Liesegang
Annette
A
Betz
Heinrich
H
Biber
Jürg
J
Murer
Heini
H
Hernando
Nati
N
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015519:Bone Density; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D005269:Femur / Q000378:metabolism; D005786:Gene Expression Regulation; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000097:blood / Q000378:metabolism* / Q000652:urine; D016226:Phosphorus, Dietary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics / Q000378:metabolism*; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; C480861:GABARAP protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010710:Phosphates; D016226:Phosphorus, Dietary; D012333:RNA, Messenger; C493555:Slc34a1 protein, mouse; C493558:Slc34a2 protein, mouse; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D012964:Sodium