Naslov
Kidney-specific inactivation of the megalin gene impairs trafficking of renal inorganic sodium phosphate cotransporter (NaPi-IIa).

Autori
Bachmann, S. ; Schlichting, U. ; Geist, B. ; Mutig, K. ; Petsch, T. ; Bačić, Deša ; Wagner, C.A. ; Kaissling, B. ; Biber, J. ; Murer, H. ; Willnow T.E.

Izvornik
Journal of the American Sociology of Nephrology (1046-6673) 15 (2004), 4; 892-900

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
megalin; edocytosis; NaPi-IIa; parathyroid hormone

Sažetak
Renal reabsorption of inorganic phosphate is mediated by the type IIa sodium phosphate cotransporter (NaPi- IIa) of the proximal tubule. Changes in renal phosphate handling are mainly attributable to altered NaPi-IIa brush border membrane (BBM) expression. Parathyroid hormone (PTH) induces inactivation of NaPi-IIa by endocytic membrane retrieval and degradation. The key elements triggering this process are not clear to date. Megalin serves as a receptor for the endocytosis of multiple ligands and is coexpressed with NaPi-IIa in the proximal tubule. Investigated was the role of megalin in the regulation of NaPi-IIa in steady state and during inactivation. Kidneys and tubular BBM fractions from mice with a renal- specific megalin gene defect and from controls were analyzed by light and electron microscopic histochemical techniques and Western blot test. Steady-state levels of NaPi-IIa in BBM were significantly enhanced, mRNA levels preserved, and phosphaturia reduced in the absence of megalin. Fluid-phase endocytosis was prevented and the apical endocytic apparatus markedly reduced. Systemic administration of PTH resulted in a defective retrieval and impaired degradation of NaPi-IIa. In vitro, the application of various stimuli of the PTH-induced signaling cascade had no effect either. Adequate steady-state expression of NaPi-IIa and the capacity of the proximal tubule cell to react on PTH-driven inactivation of NaPi-IIa by endocytosis and intracellular translocation require the presence of megalin.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA