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Accession IconGSE19778

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

Organism Icon Mus musculus
Sample Icon 6 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

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Description
The endocytic receptor megalin constitutes the main pathway for clearance of plasma proteins from the glomerular filtrate in the proximal tubules. However, little is know about the mechanisms that control receptor activity. A widely discussed hypothesis states that the intracellular domain (ICD) of megalin, released upon ligand binding, acts as a transcription regulator to suppress receptor expression - a mechanism proposed to safeguard the proximal tubules from protein overload. Here, we have put this hypothesis to the test by generating a mouse model co-expressing the soluble ICD and the full-length receptor. Despite pronounced expression in the proximal tubules, the ICD failed to exert any effects on renal proximal tubular function such as megalin expression, protein retrieval, or renal gene transcription. Thus, our data argue that the ICD does not play a role in regulation of megalin activity in vivo in the proximal tubules.
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6

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