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“N-methyl-o-aspartate receptors (NMDARs) are ligand-gated ion channels (‘ionotropic’ receptors) activated by the major excitatory neurotransmitter, L-glutamate. While the term ‘the NMDAR’ is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar. This heterogeneity was evident from early electrophysiological, pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate, it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety

of functions in the mammalian central nervous system. In this review we highlight some recent studies that have identified structural elements within GluN2 selleck products subunits that contribute to the heterogeneous biophysical properties of NMDARs, consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes, examine the evidence that NMDAR subtypes differentially contribute to the induction of long-term potentiation and long-term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype-dependency of physiological and pathophysiological

signalling.

This article is part of the Special Issue entitled ‘Glutamate Receptor-Dependent Synaptic Plasticity’. (C) 2013 Elsevier Ltd. All rights reserved.”
“Members of the tripartite Alisertib price interaction motif (TRIM) family of E3 ligases are emerging as critical regulators of innate immunity. To identify new regulators, we carried out a screen of 43 human TRIM proteins for the ability to activate NF-kappa B, AP-1, and interferon, hallmarks of many innate immune signaling pathways. We identified 16 TRIM proteins that induced NF-kappa B and/or AP-1. We found that one of these, TRIM62, functions in the TRIF branch of the TLR4 signaling pathway. Knockdown of TRIM62 in primary macrophages led to a defect in TRIF-mediated late NF-kappa B, AP-1, and interferon production after lipopolysaccharide

challenge. We click here also discovered a role for TRIM15 in the RIG-I-mediated interferon pathway upstream of MAVS. Knockdown of TRIM15 limited virus/RIG-I ligand-induced interferon production and enhanced vesicular stomatitis virus replication. In addition, most TRIM proteins previously identified to inhibit murine leukemia virus (MLV) demonstrated an ability to induce NF-kappa B/AP-1. Interfering with the NF-kappa B and AP-1 signaling induced by the antiretroviral TRIM1 and TRIM62 proteins rescued MLV release. In contrast, human immunodeficiency virus type 1 (HIV-1) gene expression was increased by TRIM proteins that induce NF-kappa B. HIV-1 resistance to inflammatory TRIM proteins mapped to the NF-kappa B sites in the HIV-1 long terminal repeat (LTR) U3 and could be transferred to MLV.