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An ABCA1-independent pathway for recycling a poorly lipidated 8.1 nm apolipoprotein E particle from glia
- Source :
- Journal of Lipid Research, Vol 52, Iss 9, Pp 1605-1616 (2011)
- Publication Year :
- 2011
- Publisher :
- Elsevier, 2011.
-
Abstract
- Lipid transport in the brain is coordinated by glial-derived lipoproteins that contain apolipoprotein E (apoE) as their primary protein. Here we show that apoE is secreted from wild-type (WT) primary murine mixed glia as nascent lipoprotein subspecies ranging from 7.5 to 17 nm in diameter. Negative-staining electron microscropy (EM) revealed rouleaux, suggesting a discoidal structure. Potassium bromide (KBr) density gradient ultracentrifugation showed that all subspecies, except an 8.1 nm particle, were lipidated. Glia lacking the cholesterol transporter ABCA1 secreted only 8.1 nm particles, which were poorly lipidated and nondiscoidal but could accept lipids to form the full repertoire of WT apoE particles. Receptor-associated-protein (RAP)-mediated inhibition of apoE receptor function blocked appearance of the 8.1 nm species, suggesting that this particle may arise through apoE recycling. Selective deletion of the LDL receptor (LDLR) reduced the level of 8.1 nm particle production by approximately 90%, suggesting that apoE is preferentially recycled through the LDLR. Finally, apoA-I stimulated secretion of 8.1 nm particles in a dose-dependent manner. These results suggest that nascent glial apoE lipoproteins are secreted through multiple pathways and that a greater understanding of these mechanisms may be relevant to several neurological disorders.
- Subjects :
- Apolipoprotein E
QD415-436
Biology
recycling
Biochemistry
Apolipoproteins E
chemistry.chemical_compound
Mice
apoE
Endocrinology
Animals
Humans
Particle Size
Cells, Cultured
Research Articles
Mice, Knockout
Cholesterol
lipoprotein
Brain
Lipid metabolism
Cell Biology
Lipid Metabolism
Cell biology
Mice, Inbred C57BL
chemistry
Receptors, LDL
Mice, Inbred DBA
ABCA1
LDL receptor
biology.protein
Density gradient ultracentrifugation
ATP-Binding Cassette Transporters
lipids (amino acids, peptides, and proteins)
Neuroglia
Lipoprotein
ATP Binding Cassette Transporter 1
Subjects
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 52
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....2d54c5118f2c19be3c17e0fec0c2235a