RGD Reference Report - A role for LRP4 in neuronal cell viability is related to apoE-binding. - Rat Genome Database

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A role for LRP4 in neuronal cell viability is related to apoE-binding.

Authors: Lu, Y  Tian, QB  Endo, S  Suzuki, T 
Citation: Lu Y, etal., Brain Res. 2007 Oct 26;1177:19-28. Epub 2007 Aug 25.
RGD ID: 8553452
Pubmed: PMID:17889837   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2007.08.035   (Journal Full-text)

The distribution pattern of apolipoprotein E (apoE) in cortical neurons in culture resembles that of low-density lipoprotein receptor-related protein 4 (LRP4). Both proteins are distributed in a punctate manner on the cell surface throughout neurons, including somas and dendrites. This finding prompted us to examine whether apoE is a ligand for LRP4 in the rat brain. ApoE and LRP4 from both Cos7 cells heterologous expressing LRP4 and brain homogenate were co-immunoprecipitated. We then examined the effect of antibody against the ligand-binding domain of LRP4 (anti-LB). Anti-LB applied to neuronal cells in culture down-regulated MAP2-immunoreactive neurons, reduced the viability of neurons and impaired synaptic structure. This effect was possibly due to a blockade of the binding of extraneuronal ligands, such as apoE/cholesterol, to LRP4 protein, since anti-LB suppressed binding of apoE to the LRP4 heterologously expressed in Cos7 cells. These results suggest that apoE is an endogenous ligand for LRP4 and may play a role as a receptor for extracellular signals, including those from glial cells, in the maintenance of the viability of neurons.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendrite morphogenesis involved_inIMP 8553452PMID:17889837UniProt 
synapse organization involved_inIMP 8553452PMID:17889837UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
plasma membrane raft located_inIDA 8553452PMID:17889837UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
apolipoprotein binding enablesIPIUniProtKB:P026508553452PMID:17889837UniProt 
signaling receptor binding enablesIPIUniProtKB:Q9QYP18553452PMID:17889837UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Apoe  (apolipoprotein E)
Lrp4  (LDL receptor related protein 4)


Additional Information