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Neuronal LRP1 Functionally Associates with Postsynaptic Proteins and Is Required for Normal Motor Function in Mice

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May, Petra, Rohlmann, Astrid, Bock, Hans H., Zurhove, Kai, Marth, Jamey D., Schomburg, Eike D., Noebels, Jeffrey L., Beffert, Uwe +3 more·2004·Molecular and Cellular Biology
DOI 10.1128/mcb.24.20.8872-8883.2004PMC PMC517900
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Abstract

The LDL receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor that is highly expressed on neurons. Neuronal LRP1 in vitro can mediate ligand endocytosis, as well as modulate signal transduction processes. However, little is known about its role in the intact nervous system. Here, we report that mice that lack LRP1 selectively in differentiated neurons develop severe behavioral and motor abnormalities, including hyperactivity, tremor, and dystonia. Since their central nervous systems appear histoanatomically normal, we suggest that this phenotype is likely attributable to abnormal neurotransmission. This conclusion is supported by studies of primary cultured neurons that show that LRP1 is present in close proximity to the N-methyl-D-aspartate (NMDA) receptor in dendritic synapses and can be coprecipitated with NMDA receptor subunits and the postsynaptic density protein PSD-95 from neuronal cell lysates. Moreover, treatment with NMDA, but not dopamine, reduces the interaction of LRP1 with PSD-95, indicating that LRP1 participates in transmitter-dependent postsynaptic responses. Together, these findings suggest that LRP1, like other ApoE receptors, can modulate synaptic transmission in the brain.

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  • LRP1 has neuronal functions and is involved in transmitter-dependent post-synaptic responses caused by its interaction with PSD-95 and NMDA.

    “The lipoprotein receptor LRP1 has neuronal functions and has been shown to be involved in transmitter-dependent post-synaptic responses caused by its interaction with the post-synaptic proteins PSD-95 and NMDA [79].”

    From Sorting nexin 17 regulates ApoER2 recycling and reelin signaling (2014) · cites this paper as [79]

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Authors
May, P., Rohlmann, A., Bock, H. H., Zurhove, K., Marth, J. D., Schomburg, E. D., Noebels, J. L., Beffert, U., Sweatt, J. D., Weeber, E. J., & Herz, J.
Affiliations
  • University of Freiburg (DE)
  • The University of Texas Southwestern Medical Center (US)
  • Howard Hughes Medical Institute (US)
  • University of Göttingen (DE)
  • Baylor College of Medicine (US)
Corresponding author
May, Petra
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
2004-10-01
Volume
24
Issue
20
Pages
8872-8883
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.24.20.8872-8883.2004
PMC
PMC517900
OpenAlex
W2112239428
Cited by
236
References
3
Citations by year
2026: 11 · 2025: 7 · 2024: 10 · 2023: 20 · 2022: 10 · 2021: 10 · 2020: 16 · 2019: 10 · 2018: 7 · 2017: 8 · 2016: 12 · 2015: 10 · 2014: 13 · 2013: 13 · 2012: 9
FWCI
2.67
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • OpenBU (Boston University) (publishedVersion)
  • FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
  • GRO (submittedVersion)
Funders
  • Alexander von Humboldt-Stiftung
  • Deutsche Forschungsgemeinschaft
  • National Institutes of Health
  • Canadian Institutes of Health Research
  • National Heart, Lung, and Blood Institute (HL-20948, R01HL063762, HL63762, R37HL063762, P01HL020948)
  • National Institute of Neurological Disorders and Stroke (NS43408, R01NS043408)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
LRP1, LDL receptor-related protein 1, postsynaptic proteins, NMDA receptor, PSD-95, synaptic transmission, motor function, hyperactivity, tremor, dystonia, apoE receptors, dendritic synapses, knockout mice
MeSH terms
Disks Large Homolog 4 Protein, Animals, Behavior, Animal, Brain, Cells, Cultured, Dopamine, Electroencephalography, Electromyography, Membrane Proteins, Mice, Transgenic, Motor Activity, Movement Disorders, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Receptors, LDL, Synapses, Tissue Distribution, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Synapsins, Long-Term Potentiation, Mice, Knockout, Excitatory Amino Acid Agonists, Coculture Techniques, Protein Subunits, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1, Intracellular Signaling Peptides and Proteins, Mice, Rats, Guanylate Kinases

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