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

MPG-Autoren
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Opazo,  Patricio
Department: Synapses-Circuits-Plasticity / Bonhoeffer, MPI of Neurobiology, Max Planck Society;

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Zitation

Hafner, A.-S., Penn, A. C., Grillo-Bosch, D., Retailleau, N., Poujol, C., Philippat, A., et al. (2015). Lengthening of the stargazin cytoplasmic tail increases synaptic transmission by promoting interaction to deeper domains of PSD-95. Neuron, 86(2), 475-489. doi:10.1016/j.neuron.2015.03.013.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-0026-DCA2-A
Zusammenfassung
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.