CNR - Institute of Neuroscience CNR
Institute of Neuroscience


Function of AMPA receptors and associated proteins in synapses

Our interest is centred on understanding the functional role of proteins associated to postsynaptic membrane of excitatory synapses in the mammalian central nervous system. In particular, we focused to study the role of various components of postsynaptic density (PSD) and of glutamate receptors. Currently, the laboratory is following a main project in the molecular regulation of glutamate receptors trafficking at synapses by Myosin motor.

AMPA receptors can cycle in and out of the postsynaptic membrane, and regulated receptor trafficking is a key factor in changing synaptic strength (Passafaro et al, 2001). There is evidence that a number of proteins that directly interact with specific AMPA receptor subunits may play important roles in AMPA receptor trafficking and targeting. AMPA receptors are heteromeric complexes composed of different combinations of four subunits, of which GluR1, GluR2 and GluR3 predominate in mature hippocampal neurons. The extracellular domain of AMPA receptors interacts with NARP, a neuronal-activity-regulated pentraxin and this interaction seems important for synaptic trafficking and clustering of receptors. We have recently demonstrated that via its extracellular N-terminal domain (NTD), AMPA receptor subunit GluR2 promotes the formation and growth of dendritic spines in cultured hippocampal neurons (Passafaro et al 2003). The mechanism involves a specific and direct interaction of N-terminal of GluR2 with N-cadherin, suggesting that GluR2 stimulates synaptic development and dendritic spines formation by a novel structural interaction at the synaptic junction (Saglietti et al, 2007). GluR1 and GluR2/3 differ in their cytoplasmic tail domains, the C-termini of which interact with distinct PDZ scaffold proteins: GluR1 with SAP97 and GluR2/3 with GRIP/ABP and PICK-1.


The C-terminal tail of GluR2 also binds to NSF and we found that NSF interaction is necessary for rapid surface delivery of the GluR2 subunits from intracellular compartments and for rapid incorporation of the receptor into the synapse (Beretta et al 2005). We also found that, in rat hippocampus, the insertion of AMPA receptors (AMPARs) into spines during synaptic plasticity requires a specific motor protein, which we identified as myosin Va. We found that myosin Va associates with AMPARs through its cargo binding domain. This interaction was enhanced by active, GTP-bound Rab11, which is also transported by the motor protein. Myosin Va mediated the CaMKII-triggered translocation of GluR1 receptors from the dendritic shaft into spines, but it was not required for constitutive GluR2 trafficking. Accordingly, myosin Va was specifically required for long-term potentiation, but not for basal synaptic transmission. In summary, we identified the specific motor protein and organelle acceptor that catalyze the directional transport of AMPARs into spines during activity-dependent synaptic plasticity (Correia et al 2008).


  • Correia SS, Bassani S, Brown TC, Lisé MF, Backos DS, El-Husseini A, Passafaro M, Esteban JA (2008) Motor protein-dependent transport of AMPA receptors into spines during long-term potentiation. Nat. Neurosci. 11:457-66.
  • Saglietti L, Dequidt C, Kamieniarz K, Rousset MC, Valnegri P, Thoumine O, Beretta F, Fagni L, Choquet D, Sala C, Sheng M, Passafaro M (2007) Extracellular interactions between GluR2 and N-cadherin in spine regulation. Neuron 54:461-77.
  • Passafaro M, Nakagawa T, Sala C, Sheng M (2003) Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2. Nature 424:677-81.
  • Passafaro M, Piëch V, Sheng M (2001) Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in hippocampal neurons. Nat. Neurosci. 4:917-26.
  • Passafaro M, Sala C, Niethammer M, Sheng M (1999) Microtubule binding by CRIPT and its potential role in the synaptic clustering of PSD-95. Nat. Neurosci. 2:1063-9.


Fondazione CARIPLO, 2003-2005

European Community, External collaborator of Dr. Carlo Sala, SYNSCAFF

Project, STREP action VI Program, 2004-2006

AIRC, 2004-2006

Compagnia San Paolo, 2005-06

Royal Society Award (International Joint Project), 2008-2010


  • M. Sheng, The Picower Center for Learning and Memory and Howard Hughes Medical Institute Massachusetts Institute of Technology, Cambridge, MA, USA.
  • D. Choquet, CNRS, Bordeaux, France.
  • L. Fagni, CNRS UPR 9023, Montpellier, France.
  • J. Esteban, Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.


PI photo

Maria Passafaro

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email  +39 02 5031 7102

Participating staff