title: Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95.
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.
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Hafner
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Penn
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
authors.forename: Dolors
authors.initials: D
authors.lastname: Grillo-Bosch
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Retailleau
authors.affiliation: Bordeaux Imaging Center, UMS 3420 CNRS, US4 INSERM, University of Bordeaux, 33000 Bordeaux, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Poujol
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Philippat
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Coussen
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sainlos
authors.affiliation: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, 33000 Bordeaux, France. Electronic address: popazo@neuro.mpg.de.
authors.forename: Patricio
authors.initials: P
authors.lastname: Opazo
authors.affiliation: 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: dchoquet@u-bordeaux.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Choquet
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D015220:Calcium Channels / Q000737:chemistry*; D002522:Chlorocebus aethiops; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: C491911:Cacng2 protein, rat; D015220:Calcium Channels; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA