Lengthening of the stargazin cytoplasmic tail increases synaptic transmission by promoting interaction to deeper domains of PSD-95

Hafner, Anne-Sophie, Penn, Andrew C, Grillo-Bosch, Dolors, Retailleau, Natacha, Poujol, Christel, Philippat, Amandine, Coussen, Françoise, Sainlos, Matthieu, Opazo, Patricio and Choquet, Daniel (2015) Lengthening of the stargazin cytoplasmic tail increases synaptic transmission by promoting interaction to deeper domains of PSD-95. Neuron, 86 (2). pp. 475-489. ISSN 0896-6273

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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science
Q Science > QH Natural history > QH0301 Biology
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Andrew Penn
Date Deposited: 07 Oct 2015 09:12
Last Modified: 08 Mar 2017 06:02
URI: http://sro.sussex.ac.uk/id/eprint/56999

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