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Lengthening of the stargazin cytoplasmic tail increases synaptic transmission by promoting interaction to deeper domains of PSD-95
journal contribution
posted on 2023-06-08, 22:41 authored by Anne-Sophie Hafner, Andrew PennAndrew Penn, Dolors Grillo-Bosch, Natacha Retailleau, Christel Poujol, Amandine Philippat, Françoise Coussen, Matthieu Sainlos, Patricio Opazo, Daniel ChoquetPSD-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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Publication status
- Published
File Version
- Published version
Journal
NeuronISSN
0896-6273Publisher
ElsevierExternal DOI
Issue
2Volume
86Page range
475-489Department affiliated with
- Neuroscience Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2015-10-07First Compliant Deposit (FCD) Date
2021-03-09Usage metrics
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