Schematic representation of the de novo synthesis pathway (A–C) and the recycling pathway (1–4) of megalin in maleate-treated cells. Megalin and RAP,
its associated protein, which acts as a chaperon, are synthesized and assembled in the rough endoplasmic reticulum (A) and are transported together
across Golgi stacks (B); megalin then reaches the apical cell surface and is inserted into microvilli and clathrin-coated pits (C). Megalin, a receptor for
many ligands, is internalized with its ligand (1) into early and late endosomes (2), where it dissociates from its ligand, which is taken up by the lysosome
(3). The receptor is recycled back (4), via dense apical tubules, to the cell surface, where it becomes competent again to bind ligands. Maleate could act at
the late endosome level (2) and also by blocking the formation of new dense apical tubules (4), which are remarkably absent in maleate-treated rats.
Source: The Renal Fanconi Syndrome, The Online Metabolic and Molecular Bases of Inherited Disease
Megalin and its ligands are trapped inside fused endosomes. Since there is no recycling of endosomes, there is a widespread dysfunction of reabsorptive
Valle
D, Beaudet
AL, Vogelstein
B, Kinzler
KW,acids,
Antonarakis
SE, etc.)
Ballabio
Gibson
K, Mitchell
The endosomes
Online Metabolic
and Molecular
mechanism; Citation:
membrane
receptors
and transporters
(glucose,
amino
phosphate,
alsoA,
will
be trapped
insideG.
these
(see text).
Bases of Inherited Disease; 2014 Available at: http://mhmedical.com/ Accessed: July 31, 2017
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