GABARAP deficiency modulates expression of NaPi-IIa in renal brush-border membranes
AUTOR(ES)
Reining, Sonja C.
FONTE
American Physiological Society
RESUMO
Renal reabsorption of inorganic phosphate (Pi) is mainly mediated by the Na+-dependent Pi-cotransporter NaPi-IIa that is expressed in the brush-border membrane (BBM) of renal proximal tubules. Regulation and apical expression of NaPi-IIa are known to depend on a network of interacting proteins. Most of the interacting partners identified so far associate with the COOH-terminal PDZ-binding motif (TRL) of NaPi-IIa. In this study GABAA receptor-associated protein (GABARAP) was identified as a novel interacting partner of NaPi-IIa applying a membrane yeast-two-hybrid system (MYTH 2.0) to screen a mouse kidney library with the TRL-truncated cotransporter as bait. GABARAP mRNA and protein are present in renal tubules, and the interaction of NaPi-IIa and GABARAP was confirmed by using glutathione S-transferase pulldowns from BBM and coimmunoprecipitations from transfected HEK293 cells. Amino acids 36–68 of GABARAP were identified as the determinant for the described interaction. The in vivo effects of this interaction were studied in a murine model. GABARAP−/− mice have reduced urinary excretion of Pi, higher Na+-dependent 32Pi uptake in BBM vesicles, and increased expression of NaPi-IIa in renal BBM compared with GABARAP+/+ mice. The expression of Na+/H+ exchanger regulatory factor (NHERF)1, an important scaffold for the apical expression of NaPi-IIa, is also increased in GABARAP−/− mice. The absence of GABARAP does not interfere with the regulation of the cotransporter by either parathyroid hormone or acute changes of dietary Pi content.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2681362Documentos Relacionados
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