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The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo

Item Type:Article
Title:The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo
Creators Name:Christ, A. and Terryn, S. and Schmidt, V. and Christensen, E.I. and Huska, M.R. and Andrade-Navarro, M.A. and Huebner, N. and Devuyst, O. and Hammes, A. and Willnow, T.E.
Abstract:Megalin-mediated endocytic uptake constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in proximal tubules. Little is known, however, about mechanisms that control megalin expression and activity in the kidney. A widely discussed hypothesis states that upon ligand binding a regulated intramembrane proteolysis releases the cytosolic domain of megalin and this fragment subsequently modulates megalin gene transcription. Here, we tested this by generating a mouse model that co-expressed both the soluble intracellular domain and full-length megalin. Despite pronounced synthesis in the proximal tubules, the soluble intracellular domain failed to exert distinct effects on renal proximal tubular function, including megalin expression, endocytic retrieval of proteins, or global renal gene transcription. Hence, our study argues that the soluble intracellular domain does not have a role in regulating the activity of megalin in the kidney.
Keywords:Endocytosis, Proteinuria, Proximal Tubule, Animals, Mice
Source:Kidney International
ISSN:0085-2538
Publisher:Nature Publishing Group (U.S.A.)
Volume:78
Number:5
Page Range:473-477
Date:September 2010
Official Publication:https://doi.org/10.1038/ki.2010.169
PubMed:View item in PubMed

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