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Katherine Roche"Molecular Mechanisms Regulating Excitatory Synapses"

Abstract :

Part I

NMDA receptors: trafficking and phosphorylationNMDA receptors play a critical role in neuronal development and synaptic plasticity. The subunit composition of NMDA receptors defines their functional properties and also regulates their trafficking and stabilization at synapses. We have focused on the distinct regulation of the NR2 subunits and have shown that subunit-specific phosphorylation and protein-protein interactions regulate NMDA receptor expression at synapses. The NR2A and NR2B subunits are highly expressed in cortex and hippocampus and are developmentally regulated. We find that phosphorylation of NR2B is important for NR2B trafficking and binding to the PSD-95 family of proteins. We also find that NR2B phosphorylation affects the balance of NR2A and NR2B expression at synapses.

Part II
AMPA receptors: trafficking and phosphorylationSynaptic AMPA receptors are dynamically regulated. Their trafficking is regulated by a variety of binding partners and posttranslational modifications. In particular, the C-termini of AMPA receptor subunits contain many phosphorylation sites and protein interaction domains. We recently showed that an intracellular loop of GluA1 is also important for regulating AMPA receptor targeting to synapses. In addition we have identified a new phosphorylation site, which regulates synaptic expression adding to the complexity of mechanisms that determine AMPA receptor localization.

Selected publications

Sanz-Clemente, A., Matta, J.A., Isaac, J.T.R., and Roche, K.W. (2010), “Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA Receptors,” Neuron, 67, 984-96.

Lu, W., Isozaki, K., Roche, K.W., and Nicoll, R.A. (2010), “Synaptic Targeting of AMPA Receptors Is Regulated by a CaMKII Site in the First Intracellular Loop of GluA1,” PNAS, 107: 22266-71 (Epub Dec. 6, 2010).

étudiants de l'IINS