ArticlePloS one2014
Low-density lipoprotein receptor-related protein 1 (LRP1) regulates the stability and function of GluA1 α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in neurons.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- LRP1 facilitates Jamestown Canyon virus infection of neurons.Journal of virology · 2025Article
- Exploration of plasma biomarkers for Alzheimer's disease by targeted lipid metabolomics based on nuclear magnetic resonance (NMR) spectroscopy.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Low to moderate ethanol exposure reduces astrocyte-induced neuroinflammatory signaling and cognitive decline in presymptomatic APP/PS1 mice.Scientific reports · 2024Article
- The Role of Impaired Receptor Trafficking in Mediating the Pathological Effects of APOE4 in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Moderate ethanol exposure reduces astrocyte-induced neuroinflammatorysignaling and cognitive decline in presymptomatic APP/PS1 mice.Research square · 2023Article
- Low-density lipoprotein receptor-related protein-1 (LRP1) in the glial lineage modulates neuronal excitability.Frontiers in network physiology · 2023Review
- Low-Density Lipoprotein Receptor LRP-2 regulates GLR-1 glutamate receptors and glutamatergic behavior inmicroPublication biology · 2023Article
- The emerging role of furin in neurodegenerative and neuropsychiatric diseases.Translational neurodegeneration · 2022Review
- Molecular Characterization of AMPA-Receptor-Containing Vesicles.Frontiers in molecular neuroscience · 2021Article
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Is a Negative Regulator of Oligodendrocyte Progenitor Cell Differentiation in the Adult Mouse Brain.Frontiers in cell and developmental biology · 2020Article
- Truncating variant burden in high-functioning autism and pleiotropic effects of LRP1 across psychiatric phenotypesJournal of psychiatry & neuroscience : JPN · 2019Article
- Advances in genetics of migraine.The journal of headache and pain · 2019Review
- AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking.Cellular and molecular life sciences : CMLS · 2019Review
- Article
- Role of LRP1 in the pathogenesis of Alzheimer's disease: evidence from clinical and preclinical studies.Journal of lipid research · 2017Review
- High Concentrations of Rosiglitazone Reduce mRNA and Protein Levels of LRP1 in HepG2 Cells.Frontiers in pharmacology · 2017Article
- Multifaceted Roles of Metzincins in CNS Physiology and Pathology: From Synaptic Plasticity and Cognition to Neurodegenerative Disorders.Frontiers in cellular neuroscience · 2017Review
- Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1.Experimental neurology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor abundantly expressed in neurons. Increasing evidence demonstrates that LRP1 regulates synaptic integrity and function at the post synapses, at least partially by regulating glutamate receptors. The α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are critical ionotropic glutamate receptors consisting of homotetramer or heterotetramer of GluA1-4 subunits and play an essential role in synaptic transmission and synaptic plasticity. Our previous work has shown that neuronal deletion of the Lrp1 gene in mice leads to decreased level of GluA1 and reduced long-term potentiation. To understand the underlying mechanism, we investigated the cellular and functional consequences of LRP1 deletion in primary neurons. Here, we show that LRP1 interacts with and regulates the cellular distribution and turnover of GluA1. LRP1 knockdown in mouse primary neurons led to accelerated turnover and decreased cell surface distribution of GluA1, which correspond to decreased phosphorylation of GluA1 at S845 and S831 sites. Decreased LRP1 expression also attenuated AMPA-evoked calcium influx and reduced GluA1-regulated neurite outgrowth and filopodia density. Our results reveal a novel mechanism by which LRP1 controls synaptic integrity and function, specifically by regulating GluA1 trafficking, phosphorylation and turnover. They further demonstrate that LRP1-GluA1 pathway may hold promises as a therapeutic target for restoring synaptic functions in neurodegenerative diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.