QBI Seminar: Molecular Mechanisms Regulating Trafficking of Synaptic Proteins
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- Full Description:
- Dr Katherine Roche,
Senior Investigator, Receptor Biology Section, National Institutes of Health - NINDS, Porter Neuroscience Research Center, Bethesda, USA
Title: Molecular Mechanisms Regulating Trafficking of Synaptic Proteins
Abstract:
The brain comprises vast numbers of neurons that communicate through synaptic contacts. Neurotransmission is a highly coordinated process in which neurotransmitters are released from presynaptic terminals and then bind to postsynaptic receptors. Our laboratory studies the molecular mechanisms underlying the trafficking and localization of synaptic proteins to postsynaptic sites. In particular, we have focused on the subunit-specific trafficking of NMDA receptors and how synaptic expression of various subtypes of NMDA receptors is regulated in development and in response to synaptic activity. We primarily study the GluN2A and GluN2B subunits, which are highly expressed in cortex and hippocampus. We find that phosphorylation of the GluN2B subunit is critical for regulating NMDA receptor binding to scaffolding proteins and receptor trafficking. Specifically, the activity dependent phosphorylation of the PDZ ligand of GluN2B is dependent on CaMKII binding to the receptor and leads to internalization of receptors. Furthermore, synaptic scaffolding proteins such as SAP102 and PSD-95 play distinct roles in the synaptic expression of NMDARs. More recently we have extended our studies to include the isoform-specific regulation of neuroligins, which are postsynaptic adhesion molecules. We find similarities with our NMDAR studies in that neuroligins are phosphorylated in an activity dependent manner and phosphorylation regulates trafficking and/or function of neuroligins at excitatory synapses.
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