Annotated protein:Low-density lipoprotein receptor-related protein 8 (LRP-8) (Apolipoprotein E receptor 2). Gene symbol: LRP8. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q924X6
antibody wiki:
SynGO gene info:SynGO data @ LRP8
Ontology domain:Biological Process
SynGO term:regulation of postsynaptic neurotransmitter receptor activity (GO:0098962)
Synapse type(s):Schaffer collateral synapse (CA3->CA1)
Annotated paper:Beffert U, et al. "Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2" Neuron. 2005 Aug 18;47(4):567-79 PMID:16102539
Figure(s):Figure 3, 6
Annotation description:Figure 3a-c: field recordings from Schaffer collateral synapses in wildtype and exon-19 mutant mice showed no significant differences of synaptic transmission, paired-pulse facilitation, and TBS-induced LTP between wild-type and Apoer2 (ex19) and Apoer2 (Δex19) mice.

Figure 3d-e: In response to Reelin, Apoer2 (ex19) mice showed a robust increase in LTP induction (Figure 3D), which was completely abrogated in the neuroanatomically indistinguishable Apoer2 (Δex19) mutant (Figure 3E).

Figure 3f: Reelin potentiates NMDA receptor-mediated pEPSPs recorded in area CA1 when AMPA receptors are blocked with CNQX. Wild-type and Apoer2 (ex19) mice showed a similarly significant increase in NMDA receptor potentials upon Reelin perfusion, which was maintained longer in the Apoer2 (ex19) mutants. By contrast, the Apoer2 (Δex19) mutant showed no elevation of NMDA receptor-dependent potentials above baseline synaptic responses.

Figure 6: immunoprecipitation assays in HEK293 cells showed Apoer2 (LRP8) can interact with proteins PSD-95 (DLG4) and NR2A.

Authors conclude: "Taken together, these data indicate that LTP enhancement by Reelin involves a molecular mechanism that is dependent upon the alternatively spliced exon 19 (of Apoer2). In addition, this mechanism involves, at least in part, the modulation of NMDA receptor functions."
Evidence tracking, Biological System:Intact tissue
Non-neuronal tissue
Evidence tracking, Protein Targeting:Genetic transformation (eg; knockout, knockin, mutations)
Over-expression
Evidence tracking, Experiment Assay:Field recordings
IP + WB/MSMS
Annotator(s):Frank Koopmans (ORCID:0000-0002-4973-5732)
Guus Smit (ORCID:0000-0002-2286-1587)
Matthijs Verhage (ORCID:0000-0002-2514-0216)
Lab:Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
Additional literature:Hippocampal LTP induction is defective in ApoER2 knockout mice @ PMID:12167620
SynGO annotation ID:5039
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology