Lrp4 domains differentially regulate limb/brain development and synaptic plasticity
Open accessAbstract
Apolipoprotein E (ApoE) genotype is the strongest predictor of Alzheimer's Disease (AD) risk. ApoE is a cholesterol transport protein that binds to members of the Low-Density Lipoprotein (LDL) Receptor family, which includes LDL Receptor Related Protein 4 (Lrp4). Lrp4, together with one of its ligands Agrin and its co-receptors Muscle Specific Kinase (MuSK) and Amyloid Precursor Protein (APP), regulates neuromuscular junction (NMJ) formation. All four proteins are also expressed in the adult brain, and APP, MuSK, and Agrin are required for normal synapse function in the CNS. Here, we show that Lrp4 is also required for normal hippocampal plasticity. In contrast to the closely related Lrp8/Apoer2, the intracellular domain of Lrp4 does not appear to be necessary for normal expression and maintenance of long-term potentiation at central synapses or for the formation and maintenance of peripheral NMJs. However, it does play a role in limb development.
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Mice with a hypomorphic Lrp4 allele show the same reduction in synaptic transmission and long-term potentiation.
“this finding is mimicked in mice carrying a hypomorphic allele for Lrp4 [94]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [94]
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References 42 · Cited by 28
- Authors
- Pohlkamp, T., Durakoglugil, M., Lane-Donovan, C., Xian, X., Johnson, E. B., Hammer, R. E., & Herz, J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Pohlkamp, Theresa
- Herz, Joachim
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-02-17
- Volume
- 10
- Issue
- 2
- Pages
- e0116701
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4331535
- OpenAlex
- W2082809168
- Cited by
- 28
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 3 · 2018: 5 · 2017: 5 · 2016: 1
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Health Assistance Foundation
- Ted Nash Long Life Foundation
- National Institutes of Health (HL63762)
- National Institute on Aging (F30AG047799)
- National Heart, Lung, and Blood Institute (R01HL063762, R37HL063762)
- 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 › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- LRP4, LDL receptor family, apolipoprotein E, Alzheimer's disease, agrin, muscle-specific kinase, amyloid precursor protein, neuromuscular junction formation, hippocampal plasticity, synaptic plasticity, long-term potentiation, limb development, cytoplasmic domain
- MeSH terms
- Animals, Brain, Extremities, Humans, Mice, Transgenic, Mutation, Neuronal Plasticity, Phenotype, Long-Term Potentiation, Limb Deformities, Congenital, Mice, Knockout, LDL-Receptor Related Proteins, Organogenesis, Mice, Protein Interaction Domains and Motifs
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