RACK1 is involved in β-amyloid impairment of muscarinic regulation of GABAergic transmission
Open accessAbstract
RACK1 (receptor for activated C-kinase 1), an anchoring protein that shuttles activated PKC to cellular membranes, plays an important role in PKC-mediated signal transduction pathways. A significant loss of RACK1 has been found in the brain of aging animals and Alzheimer's disease (AD) patients, which implicates the potential involvement of RACK1 in altered PKC activation associated with dementia. Our previous studies have demonstrated that GABAergic inhibition in prefrontal cortex, which is important for cognitive processes like "working memory", is regulated by muscarinic receptors via a PKC-dependent mechanism, and this effect is impaired by β-amyloid peptide (Aβ). In this study, we found that Aβ oligomers decreased RACK1 distribution in the membrane fraction of cortical neurons. Moreover, overexpression of RACK1 rescued the effect of muscarinic receptors on GABAergic transmission in Aβ-treated cortical cultures in vitro and Aβ-injected cortical neurons in vivo. These results suggest that the Aβ-induced loss of RACK1 distribution in the cell membrane may underlie the Aβ impairment of muscarinic regulation of PKC and GABAergic transmission. Thus, RACK1 provides a potential therapeutic target that can restore some of the impaired cellular processes by Aβ.
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Aβ-induced loss of RACK1 distribution in membrane fraction of cortical neurons underlies impairment of muscarinic regulation of PKC.
“Aβ-induced loss of RACK1 (an anchoring protein for activated PKC) distribution in the membrane fraction of cortical neurons is found to underlie the impairment of muscarinic regulation of PKC 247.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [247]
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- Authors
- Liu, W., Dou, F., Feng, J., & Yan, Z.
- Affiliations
- University at Buffalo, State University of New York (US)
- Beijing Normal University (CN)
- Corresponding author
- Yan, Zhen
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 32
- Issue
- 10
- Pages
- 1818-1826
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2888795
- OpenAlex
- W2114459079
- Cited by
- 33
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2019: 1 · 2017: 2 · 2016: 6 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China (30528009, NSFC 30600099)
- National Institutes of Health (AG21923, MH84233)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- RACK1, amyloid-beta, muscarinic receptors, GABAergic neurotransmission, protein kinase C, Alzheimer's disease, prefrontal cortex, cortical neurons, amyloid-beta oligomers, working memory, therapeutic target
- MeSH terms
- Receptors for Activated C Kinase, Analysis of Variance, Animals, Animals, Newborn, Carbachol, Cells, Cultured, Cerebral Cortex, Embryo, Mammalian, gamma-Aminobutyric Acid, Gene Expression Regulation, Synaptic Transmission, Neurons, Peptide Fragments, Protein Kinase C, Receptors, Muscarinic, Subcellular Fractions, Transfection, Amyloid beta-Peptides, Patch-Clamp Techniques, Cholinergic Agonists, GTP-Binding Proteins, RNA, Small Interfering, Green Fluorescent Proteins, Rats, Inhibitory Postsynaptic Potentials, In Vitro Techniques
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