Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95.
Neuron. 2015-04-01; 86(2): 475-489
DOI: 10.1016/j.neuron.2015.03.013
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1. Neuron. 2015 Apr 22;86(2):475-89. doi: 10.1016/j.neuron.2015.03.013. Epub 2015
Apr 2.
Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by
Promoting Interaction to Deeper Domains of PSD-95.
Hafner AS(1), Penn AC(1), Grillo-Bosch D(1), Retailleau N(1), Poujol C(2),
Philippat A(1), Coussen F(1), Sainlos M(1), Opazo P(3), Choquet D(4).
Author information:
(1)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience,
UMR 5297, 33000 Bordeaux, France.
(2)Bordeaux Imaging Center, UMS 3420 CNRS, US4 INSERM, University of Bordeaux,
33000 Bordeaux, France.
(3)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience,
UMR 5297, 33000 Bordeaux, France. Electronic address: .
(4)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience,
UMR 5297, 33000 Bordeaux, France; Bordeaux Imaging Center, UMS 3420 CNRS, US4
INSERM, University of Bordeaux, 33000 Bordeaux, France. Electronic address:
.
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.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2015.03.013
PMID: 25843401 [Indexed for MEDLINE]