Linked Life Data

15705569

Source:http://linkedlifedata.com/resource/pubmed/id/15705569

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2005-4-11
pubmed:abstractText
The low density lipoprotein receptor-related protein (LRP) is a approximately 600-kDa multifunctional endocytic receptor that is highly expressed in the brain. LRP and its ligands apolipoprotein E, alpha2-macroglobulin, and beta-amyloid precursor protein (APP), are genetically linked to Alzheimer disease and are found in characteristic plaque deposits in brains of patients with Alzheimer disease. To identify which extracellular domains of LRP interact with APP, we used minireceptors of each of the individual LRP ligand binding domains and assessed their ability to bind and degrade a soluble APP fragment. LRP minireceptors containing ligand binding domains II and IV, but not I or III, interacted with APP. To test whether APP trafficking is directly related to the rapid endocytosis of LRP, we generated stable Chinese hamster ovary cell lines expressing either a wild-type LRP minireceptor or its endocytosis mutants. Chinese hamster ovary cells stably expressing wild-type LRP minireceptor had less cell surface APP than pcDNA3 vector-transfected cells, whereas those stably expressing endocytosis-defective LRP minireceptors accumulated APP at the cell surface. We also found that the steady-state levels of the amyloid beta-peptides (Abeta) is dictated by the relative expression levels of APP and LRP, probably reflecting the dual roles of LRP in both Abeta production and clearance. Together, these data establish a relationship between LRP rapid endocytosis and APP trafficking and proteolytic processing to generate Abeta.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15464-70
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15705569-Amino Acid Sequence, pubmed-meshheading:15705569-Amyloid beta-Peptides, pubmed-meshheading:15705569-Amyloid beta-Protein Precursor, pubmed-meshheading:15705569-Animals, pubmed-meshheading:15705569-CHO Cells, pubmed-meshheading:15705569-Cell Line, pubmed-meshheading:15705569-Cricetinae, pubmed-meshheading:15705569-Culture Media, Conditioned, pubmed-meshheading:15705569-DNA, Complementary, pubmed-meshheading:15705569-Endocytosis, pubmed-meshheading:15705569-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:15705569-Flow Cytometry, pubmed-meshheading:15705569-Humans, pubmed-meshheading:15705569-Immunoblotting, pubmed-meshheading:15705569-Immunoprecipitation, pubmed-meshheading:15705569-Kinetics, pubmed-meshheading:15705569-Low Density Lipoprotein Receptor-Related Protein-1, pubmed-meshheading:15705569-Molecular Sequence Data, pubmed-meshheading:15705569-Mutation, pubmed-meshheading:15705569-Signal Transduction, pubmed-meshheading:15705569-Time Factors, pubmed-meshheading:15705569-Transfection
pubmed:year
2005
pubmed:articleTitle
Rapid endocytosis of the low density lipoprotein receptor-related protein modulates cell surface distribution and processing of the beta-amyloid precursor protein.
pubmed:affiliation
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural