Premium
Megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid
Author(s) -
BentoAbreu André,
Velasco Ana,
PoloHernández Erica,
PérezReyes Pedro Luis,
Tabernero Arantxa,
Medina José M.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05462.x
Subject(s) - oleic acid , internalization , albumin , astrocyte , chemistry , neurotrophic factors , biochemistry , ciliary neurotrophic factor , serum albumin , neurotrophin , microbiology and biotechnology , receptor , biology , endocrinology , central nervous system
We have previously shown that the uptake and transcytosis of albumin in astrocytes promote the synthesis of the neurotrophic factor oleic acid. Although the mechanism by which albumin induces oleic acid synthesis is well known, the mechanism of albumin uptake in astrocytes remains unknown. In this work, we found that astrocytes express megalin, an endocytic receptor for multiple ligands including albumin. In addition, when the activity of megalin is blocked by specific antibodies or by silencing megalin with specific siRNA, albumin binding and internalization is strongly reduced indicating that megalin is required for albumin binding and internalization in the astrocyte. Since the uptake of albumin in astrocytes aims at synthesizing the neurotrophic factor oleic acid, we tested the ability of megalin‐silenced astrocytes to synthesize and release oleic acid in the presence of albumin. Our results showed that the amount of oleic acid found in the extracellular medium of megalin‐silenced astrocytes was strongly reduced as compared with their controls. Together, the results of this work indicate that megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid. Consequently, the possible involvement of albumin in the holoprosencephalic syndrome observed in megalin‐deficient mice is suggested.