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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 Choquet
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Neuron

ISSN

0896-6273

Publisher

Elsevier

Issue

2

Volume

86

Page range

475-489

Department affiliated with

  • Neuroscience Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2015-10-07

First Compliant Deposit (FCD) Date

2021-03-09

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