Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95
Open accessAbstract
PSD-95 is a prominent organizer of the postsynaptic density (PSD) that can present a filamentous orientation perpendicular to the plasma membrane. Interactions between PSD-95 and transmembrane proteins might be particularly sensitive to this orientation, as "long" cytoplasmic tails might be required to reach deeper PSD-95 domains. Extension/retraction of transmembrane protein C-tails offer a new way of regulating binding to PSD-95. Using stargazin as a model, we found that enhancing the apparent length of stargazin C-tail through phosphorylation or by an artificial linker was sufficient to potentiate binding to PSD-95, AMPAR anchoring, and synaptic transmission. A linear extension of stargazin C-tail facilitates binding to PSD-95 by preferentially engaging interaction with the farthest located PDZ domains regarding to the plasma membrane, which present a greater affinity for the stargazin PDZ-domain-binding motif. Our study reveals that the concerted orientation of the stargazin C-tail and PSD-95 is a major determinant of synaptic strength.
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CaMKII phosphorylation of TARP serines neutralizes charge, releasing the CTD and providing access to the PDZ domains of PSD-95.
“CaMKII phosphorylation of the serines neutralizes the charge, releasing the CTD and providing access to the PDZ domains of PSD-95 (284, 285, 287).”
From Synaptic memory and CaMKII (2023) · cites this paper as [287]
Cites
Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms
Chen, L., Chetkovich, D. M., Petralia, R. S., Sweeney, N. T., Kawasaki, Y., Wenthold, R. J., Bredt, D. S., & Nicoll, R. A. (2000) · Nature · doi:10.1038/35050030 · Cited by 1,111 · see citing works
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Stein, V., House, D. R. C., Bredt, D. S., & Nicoll, R. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05503.2003 · Cited by 341 · see citing works
Regulation of AMPA receptor surface diffusion by PSD-95 slots
Opazo, P., Sainlos, M., & Choquet, D. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.10.010 · Cited by 234 · see citing works
Self-citationA three-step model for the synaptic recruitment of AMPA receptors
Opazo, P., & Choquet, D. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2010.08.014 · Cited by 190 · see citing works
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Molecular Mechanisms of Early and Late LTP
Baltaci, S. B., Mogulkoc, R., & Baltaci, A. K. (2019) · Neurochemical Research · doi:10.1007/s11064-018-2695-4 · Cited by 152 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“Early studies examining the effects of phosphonull and phos-phomimic mutations of the serines suggested a role of these serines in AMPAR traf fi cking and LTP (283 – 287).”
BackgroundWarnet, X. L., Bakke Krog, H., Sevillano‐Quispe, O. G., Poulsen, H., & Kjaergaard, M. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14842 · Cited by 50 · see citing works
- Authors
- Hafner, A.-S., Penn, A. C., Grillo-Bosch, D., Retailleau, N., Poujol, C., Philippat, A., Coussen, F., Sainlos, M., Opazo, P., & Choquet, D.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Opazo, Patricio
- Choquet, Daniel
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 86
- Issue
- 2
- Pages
- 475-489
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2059353249
- Cited by
- 101
- References
- 5
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 19 · 2017: 6 · 2016: 4 · 2015: 2
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- Figshare (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- stargazin, PSD-95, synaptic transmission, postsynaptic density, PDZ domain, protein phosphorylation, synaptic efficacy, protein-protein interaction
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Chlorocebus aethiops, Hippocampus, Membrane Proteins, Synaptic Transmission, Neurons, Phosphorylation, Calcium Channels, Receptors, AMPA, COS Cells, Amino Acid Motifs, Intracellular Signaling Peptides and Proteins, Rats
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