http://hdl.handle.net/1842/1672 2013-05-20T11:54:10Z http://hdl.handle.net/1842/742 Title: Proteomic analysis of NMDA receptor–adhesion protein signaling complexes Authors: Husi, Holger; Ward, Malcolm A; Choudhary, Jyoti S; Blackstock, Walter P; Grant, Seth GN Abstract: N-methyl-D-aspartate receptors (NMDAR) mediate long-lasting changes in synapse strength via downstream signaling pathways. We report proteomic characterization with mass spectrometry and immunoblotting of NMDAR multiprotein complexes (NRC) isolated from mouse brain. The NRC comprised 77 proteins organized into receptor, adaptor, signaling, cytoskeletal and novel proteins, of which 30 are implicated from binding studies and another 19 participate in NMDAR signaling. NMDAR and metabotropic glutamate receptor subtypes were linked to cadherins and L1 cell-adhesion molecules in complexes lacking AMPA receptors. These neurotransmitter– adhesion receptor complexes were bound to kinases, phosphatases, GTPase-activating proteins and Ras with effectors including MAPK pathway components. Several proteins were encoded by activity-dependent genes. Genetic or pharmacological interference with 15 NRC proteins impairs learning and with 22 proteins alters synaptic plasticity in rodents. Mutations in three human genes (NF1, Rsk-2, L1) are associated with learning impairments, indicating the NRC also participates in human cognition. 2000-07-01T00:00:00Z http://hdl.handle.net/1842/740 Title: Flies put the buzz back into long-term-potentiation Authors: Paulsen, Ole; Morris, Richard G M Abstract: Two new papers show that an atypical protein kinase C may mediate the maintenance of long-term potentiation in the mouse hippocampus and of associative memory in Drosophila. 2002-04-01T00:00:00Z http://hdl.handle.net/1842/738 Title: Reversible neural inactivation reveals hippocampal particin several memory processesipation Authors: Riedel, G; Micheau, J; Lam, A G M; Roloff, E.v.L.; Martin, Stephen J; Bridge, H; de Hoz, L; Poeschel, B; McCulloch, J; Morris, Richard G M Abstract: Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes—encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage. 1999-10-01T00:00:00Z http://hdl.handle.net/1842/737 Title: Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene Authors: Mack, Till GA; et al Abstract: Axons and their synapses distal to an injury undergo rapid Wallerian degeneration, but axons in the C57BL/WldS mouse are protected. The degenerative and protective mechanisms are unknown. We identified the protective gene, which encodes an N-terminal fragment of ubiquitination factor E4B (Ube4b) fused to nicotinamide mononucleotide adenylyltransferase (Nmnat), and showed that it confers a dose-dependent block of Wallerian degeneration. Transected distal axons survived for two weeks, and neuromuscular junctions were also protected. Surprisingly, the Wld protein was located predominantly in the nucleus, indicating an indirect protective mechanism. Nmnat enzyme activity, but not NAD+ content, was increased fourfold in WldS tissues. Thus, axon protection is likely to be mediated by altered ubiquitination or pyridine nucleotide metabolism. 2001-12-01T00:00:00Z