| Annotated protein: | Prolow-density lipoprotein receptor-related protein 1 (LRP-1) (Alpha-2-macroglobulin receptor) (A2MR) (CD antigen CD91) [Cleaved into: Low-density lipoprotein receptor-related protein 1 85 kDa subunit (LRP-85); Low-density lipoprotein receptor-related protein 1 515 kDa subunit (LRP-515); Low-density lipoprotein receptor-related protein 1 intracellular domain (LRPICD)]. Gene symbol: LRP1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q91ZX7 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ LRP1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic neurotransmitter receptor endocytosis (GO:0099149) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Nakajima C, et al. "Low density lipoprotein receptor-related protein 1 (LRP1) modulates N-methyl-D-aspartate (NMDA) receptor-dependent intracellular signaling and NMDA-induced regulation of postsynaptic protein complexes" J Biol Chem. 2013 Jul 26;288(30):21909-23 PMID:23760271 |
| Figure(s): | Figure 4, 5, 6 |
| Annotation description: | Shedding of the LRP1 extracellular domain is the regulated step during the proteolytical processing of LRP1, and cleavage by the γ-secretase complex to release the LRP1 intracellular domain follows constitutively. Figure 4: activation of NMDA receptors accelerates the rate of LRP1 proteolytical processing, but NMDA-induced increase of LRP1 cleavage does not involve direct binding of NMDA to LRP1. Figure 5: "LRP1 facilitates NMDA-induced degradation of PSD-95, and in the absence of LRP1, ubiquitinated PSD-95 Is increased, whereas NMDA-induced GluA1 internalization is reduced. ... Furthermore, NMDA treatment led to the accumulation of ubiquitinated PSD-95 in LRP1-deficient cortical neurons (Fig. 5B, a and b). Interestingly, treatment with the proteasome inhibitors MG-132 and epoxomicin blocked NMDA-induced degradation of PSD-95 neither in LRP1-deficient nor in control cells (data not shown). This indicates that degradation was non-proteasomal and that ubiquitination served a purpose other than delivery of PSD-95 to the proteasome, as found in an earlier work by Bianchetta et al. (26), who linked ubiquitination of PSD-95 to its interaction with the endocytosis machinery of neurons." Figure 6: "Examination of the AMPA receptor subunit GluA1, on the other hand, demonstrated greatly reduced NMDA-induced internalization of this receptor in the absence of LRP1 both by measurement of internalized protein and by biotin labeling of surface-localized subunits (Fig. 6A, a and b). Endocytosis of GluA1 and LRP1 followed a similar time course (Fig. 6A, a and c). Furthermore, we could show by co-immunoprecipitation from neuronal lysates that there is a physical interaction between LRP1 and GluA1 (Fig. 6B) that might play a role, directly or through other interacting proteins, in the effect of LRP1 on NMDA-induced GluA1 endocytosis." |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Antagonist / agonist Antibody (detection) Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | 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: | LRP1 modulates NMDA receptor-mediated calcium currents @ PMID:18321860 LRP is known to be involved in regulating endocytosis (here demonstrated in liver) @ PMID:9449704 "Here, we show that endogenous PSD-95 can be coprecipitated with LRP1 from cultured primary neurons. Treatment of cells with NMDA reduces the amount of PSD-95 that is brought down with LRP1, indicating a function-dependent interaction of the two proteins. In addition, we demonstrate that NMDA receptor subunits also coprecipitate with neuronal LRP1 and that they colocalize with LRP1 in neurons." @ PMID:15456862 |
| SynGO annotation ID: | 5057 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |