Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation

Fabrice Raynaud, Andrea Janossy, Janine Dahl, Federica Bertaso, Julie Perroy, Annie Varrault, Michel Vidal, Paul F Worley, Tobias M. Boeckers, Joël Bockaert, Philippe Marin, Laurent Fagni, Vincent Homburger

Research output: Contribution to journalArticle

Abstract

Synaptic long-term potentiation (LTP) is a key mechanism involved in learning and memory, and its alteration is associated with mental disorders. Shank3 is a major postsynaptic scaffolding protein that orchestrates dendritic spine morphogenesis, and mutations of this protein lead to mental retardation and autism spectrum disorders. In the present study we investigated the role of a new Shank3-associated protein in LTP. We identified the Rho-GAP interacting CIP4 homolog 2 (Rich2) as a new Shank3 partner by proteomic screen. Using single-cell bioluminescence resonance energy transfer microscopy, we found that Rich2-Shank3 interaction is increased in dendritic spines of mouse cultured hippocampal neurons during LTP.Wefurther characterized Rich2 as an endosomal recycling protein that controls AMPA receptor GluA1 subunit exocytosis and spine morphology. Knock-down of Rich2 with siRNA, or disruption of the Rich2-Shank3 complex using an interfering mimetic peptide, inhibited the dendritic spine enlargement and the increase in GluA1 subunit exocytosis typical of LTP. These results identify Rich2-Shank3 as a new postsynaptic protein complex involved in synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)9699-9715
Number of pages17
JournalJournal of Neuroscience
Volume33
Issue number23
DOIs
StatePublished - 2013

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AMPA Receptors
Long-Term Potentiation
Dendritic Spines
Exocytosis
Proteins
Neuronal Plasticity
Energy Transfer
Morphogenesis
Mental Disorders
Intellectual Disability
Proteomics
Small Interfering RNA
Microscopy
Spine
Learning
Neurons
Peptides
Mutation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Raynaud, F., Janossy, A., Dahl, J., Bertaso, F., Perroy, J., Varrault, A., ... Homburger, V. (2013). Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation. Journal of Neuroscience, 33(23), 9699-9715. https://doi.org/10.1523/JNEUROSCI.2725-12.2013

Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation. / Raynaud, Fabrice; Janossy, Andrea; Dahl, Janine; Bertaso, Federica; Perroy, Julie; Varrault, Annie; Vidal, Michel; Worley, Paul F; Boeckers, Tobias M.; Bockaert, Joël; Marin, Philippe; Fagni, Laurent; Homburger, Vincent.

In: Journal of Neuroscience, Vol. 33, No. 23, 2013, p. 9699-9715.

Research output: Contribution to journalArticle

Raynaud, F, Janossy, A, Dahl, J, Bertaso, F, Perroy, J, Varrault, A, Vidal, M, Worley, PF, Boeckers, TM, Bockaert, J, Marin, P, Fagni, L & Homburger, V 2013, 'Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation', Journal of Neuroscience, vol. 33, no. 23, pp. 9699-9715. https://doi.org/10.1523/JNEUROSCI.2725-12.2013
Raynaud, Fabrice ; Janossy, Andrea ; Dahl, Janine ; Bertaso, Federica ; Perroy, Julie ; Varrault, Annie ; Vidal, Michel ; Worley, Paul F ; Boeckers, Tobias M. ; Bockaert, Joël ; Marin, Philippe ; Fagni, Laurent ; Homburger, Vincent. / Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 23. pp. 9699-9715.
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