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

AS Hafner, AC Penn, D Grillo-Bosch, N Retailleau… - Neuron, 2015 - cell.com
AS Hafner, AC Penn, D Grillo-Bosch, N Retailleau, C Poujol, A Philippat, F Coussen…
Neuron, 2015cell.com
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 …
Summary
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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