Ras and Rap control AMPA receptor trafficking during synaptic plasticity
Open accessAbstract
Recent studies show that AMPA receptor (-R) trafficking is important in synaptic plasticity. However, the signaling controlling this trafficking is poorly understood. Small GTPases have diverse neuronal functions and their perturbation is responsible for several mental disorders. Here, we examine the small GTPases Ras and Rap in the postsynaptic signaling underlying synaptic plasticity. We show that Ras relays the NMDA-R and CaMKII signaling that drives synaptic delivery of AMPA-Rs during long-term potentiation. In contrast, Rap mediates NMDA-R-dependent removal of synaptic AMPA-Rs that occurs during long-term depression. Ras and Rap exert their effects on AMPA-Rs that contain different subunit composition. Thus, Ras and Rap, whose activity can be controlled by postsynaptic enzymes, serve as independent regulators for potentiating and depressing central synapses.
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Rho-Rock and Ras-ERK signaling pathways lower the threshold for LTP in neighboring spines.
“In addition, Rho-Rock and Ras-ERK signaling pathways lower the threshold for LTP in neighboring spines (Zhu et al., 2002; Harvey and Svoboda, 2007; Harvey et al., 2008; Lee et al., 2009).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Zhu et al., 2002
Downstream of CaMKII, Ras and Rho GTPases are important for regulating spine morphology and synaptic strength.
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From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Zhu et al., 2002
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“Importantly, Rap1 regulates NMDAR-dependent AMPAR endocytosis during LTD via p38 MAPK [42].”
From Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD (2009) · cites this paper as [42]
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- Authors
- Zhu, J. J., Qin, Y., Zhao, M., Van Aelst, L., & Malinow, R.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Malinow, Roberto
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 110
- Issue
- 4
- Pages
- 443-455
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2136008443
- Cited by
- 769
- References
- 5
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 18 · 2023: 13 · 2022: 17 · 2021: 19 · 2020: 33 · 2019: 27 · 2018: 30 · 2017: 25 · 2016: 28 · 2015: 25 · 2014: 42 · 2013: 36 · 2012: 45
- FWCI
- 14.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Ras, rap, AMPA receptor trafficking, synaptic plasticity, long-term potentiation, long-term depression, NMDA receptor signaling, CaMKII, small GTPases, postsynaptic signaling, AMPA receptor subunit composition, synapses
- MeSH terms
- Animals, Enzyme Inhibitors, Hippocampus, Luminescent Proteins, Male, Mutation, Neural Inhibition, Synaptic Transmission, Organ Culture Techniques, Subcellular Fractions, Synapses, Synaptic Membranes, Signal Transduction, Magnesium Chloride, Protein Structure, Tertiary, Long-Term Potentiation, Receptors, AMPA, ras Proteins, Excitatory Amino Acid Antagonists, Mitogen-Activated Protein Kinase 1, rap GTP-Binding Proteins, Mitogen-Activated Protein Kinases, Protein Transport, p38 Mitogen-Activated Protein Kinases, Green Fluorescent Proteins, Rats
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