Rho-GTPase-activating Protein Interacting with Cdc-42-interacting Protein 4 Homolog 2 (Rich2) - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2014

Rho-GTPase-activating Protein Interacting with Cdc-42-interacting Protein 4 Homolog 2 (Rich2)

F. Raynaud
Enora Moutin
Vincent Compan
  • Fonction : Auteur
Caroline Clerté
  • Fonction : Auteur
Nathalie Bouquier
  • Fonction : Auteur
Gilles Labesse
Matthew Ferguson
  • Fonction : Auteur
Laurent Fagni
  • Fonction : Auteur
Catherine Royer
  • Fonction : Auteur
Julie Perroy
Susanne Schmidt
Janine Dahl
  • Fonction : Auteur
Federica Bertaso
Tobias Boeckers
  • Fonction : Auteur
Vincent Homburger
  • Fonction : Auteur

Résumé

Quantitative spatio-temporal characterization of protein interactions in living cells remains a major challenge facing modern biology. We have investigated in living neurons the spatial dependence of the stoichiometry of interactions between two core proteins of the NMDA receptor-associated scaffolding complex, GKAP and DLC2, using a novel variation of Fluorescence Fluctuation Microscopy called two-photon scanning Number and Brightness (sN&B). We found that dimerization of DLC2 was required for its interaction with GKAP, which in turn potentiated GKAP self-association. In dendritic shaft, the DLC2-GKAP hetero-oligomeric complexes were composed mainly of 2 DLC2 and 2 GKAP monomers, while in spines, the hetero-complexes were much larger, with an average of ∼16 DLC2 and ∼13 GKAP. Disruption of the GKAP-DLC2 interaction strongly destabilized the oligomers, decreasing the spine-preferential localization of GKAP and inhibiting NMDA receptor activity. Hence, DLC2 serves a hub function in the control of glutamatergic transmission via ordering of GKAP-containing complexes in dendritic spines. Beyond illuminating the role of DLC2–GKAP interactions in glutamergic signalling, these data underscore the power of the sN&B approach for quantitative spatio-temporal imaging of other important protein complexes.

Dates et versions

hal-03674325 , version 1 (20-05-2022)

Identifiants

Citer

F. Raynaud, Enora Moutin, Vincent Compan, Caroline Clerté, Nathalie Bouquier, et al.. Rho-GTPase-activating Protein Interacting with Cdc-42-interacting Protein 4 Homolog 2 (Rich2). Journal of Biological Chemistry, 2014, 289 (5), pp.2600-2609. ⟨10.1074/jbc.m113.534636⟩. ⟨hal-03674325⟩
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