Document Detail


Albumin endocytosis via megalin in astrocytes is caveola- and Dab-1 dependent and is required for the synthesis of the neurotrophic factor oleic acid.
MedLine Citation:
PMID:  19656258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The synthesis and release of the neurotrophic factor oleic acid requires internalization of albumin into the astrocyte, which is mediated by megalin. In this study, we show that the binding and internalization of albumin involve its interaction with megalin, caveolin-1, caveolin-2 and cavin, but not with clathrin in astrocytes from primary culture. Electron microscopy analyses revealed albumin-gold complexes localized in caveolae, but not in clathrin-coated vesicles. Neither chlorpromazine nor silencing clathrin expression modified albumin uptake. Silencing caveolin-1 strongly reduced the binding and internalization of albumin and the distribution of megalin in the plasma membrane. However, silencing caveolin-2 only decreased albumin internalization, suggesting that caveolin-1 is responsible for megalin recruitment to the caveolae and that caveolin-2 participates in caveolae internalization. In most tissues, the cytosolic adaptor protein disabled (Dab)-2 connects megalin to clathrin, astrocytes lack Dab-2; instead, they express Dab-1, which interacts with caveolin-1 and megalin and is required for albumin internalization. The transcytosis of albumin in astrocytes, including the passage through the endoplasmic reticulum, which is a compulsory step for oleic acid synthesis, was confirmed by electron microscopy analyses. Thus, whereas silencing clathrin did not modify the synthesis and release of oleic acid, the knock-down of caveolin-1, caveolin-2 and Dab-1 strongly reduced the synthesis and release of this neurotrophic factor. In conclusion, caveola-mediated endocytosis of albumin requires megalin and the adaptor protein Dab-1 in cultured astrocytes. Albumin endocytosis may be a key step in brain development because it stimulates the synthesis of oleic acid, which in turn promotes neuronal differentiation.
Authors:
André Bento-Abreu; Ana Velasco; Erica Polo-Hernández; Concepción Lillo; Renata Kozyraki; Arantxa Tabernero; José M Medina
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-25
Journal Detail:
Title:  Journal of neurochemistry     Volume:  111     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-09-23     Completed Date:  2009-10-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  49-60     Citation Subset:  IM    
Affiliation:
Departamento de Bioquímica y Biología Molecular, Instituto de Neurociencias de Castilla y León (INCYL), Universidad de Salamanca, Salamanca, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics,  metabolism*
Albumins / metabolism*
Analysis of Variance
Animals
Astrocytes / drug effects,  metabolism*,  ultrastructure
Caveolae / metabolism*
Cells, Cultured
Chlorpromazine / pharmacology
Chromatography, High Pressure Liquid / methods
Dopamine Antagonists / pharmacology
Endocytosis / drug effects,  physiology*
Immunoprecipitation
LDL-Receptor Related Protein 2 / genetics,  metabolism*
Microscopy, Electron, Transmission / methods
Nerve Tissue Proteins / genetics,  metabolism*
Oleic Acid / metabolism*
Prosencephalon / cytology
RNA, Small Interfering / pharmacology
Rats
Rats, Wistar
Transfection / methods
Transferrin / metabolism
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Albumins; 0/Dopamine Antagonists; 0/LDL-Receptor Related Protein 2; 0/Nerve Tissue Proteins; 0/RNA, Small Interfering; 0/disabled-1 protein, rat; 11096-37-0/Transferrin; 112-80-1/Oleic Acid; 50-53-3/Chlorpromazine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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