Transmembrane Adaptor Proteins Positively Regulating the Activation of Lymphocytes

Engagement of the immunoreceptors initiates signaling cascades resulting in lymphocyte activation and differentiation to effector cells, which are essential for the elimination of pathogens from the body. For the transduction of these immunoreceptor-mediated signals, several linker proteins termed transmembrane adaptor proteins (TRAPs) were shown to be required. TRAPs serve as platforms for the assembly and membrane targeting of the specific signaling proteins. Among seven TRAPs identified so far, LAT and LIME were shown to act as a positive regulator in TCR-mediated signaling pathways. In this review, we will discuss the functions of LAT and LIME in modulating T cell development, activation and differentiation

The many faces of nitric oxide: cytotoxic, cytoprotective or both

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74882/1/j.1365-2982.2007.00958.x.pd

Recruitment of Slp-76 to the Membrane and Glycolipid-Enriched Membrane Microdomains Replaces the Requirement for Linker for Activation of T Cells in T Cell Receptor Signaling

Two hematopoietic-specific adapters, src homology 2 domain–containing leukocyte phosphoprotein of 76 kD (SLP-76) and linker for activation of T cells (LAT), are critical for T cell development and T cell receptor (TCR) signaling. Several studies have suggested that SLP-76 and LAT function coordinately to promote downstream signaling. In support of this hypothesis, we find that a fraction of SLP-76 localizes to glycolipid-enriched membrane microdomains (GEMs) after TCR stimulation. This recruitment of SLP-76 requires amino acids 224–244. The functional consequences of targeting SLP-76 to GEMs for TCR signaling are demonstrated using a LAT/SLP-76 chimeric protein. Expression of this construct reconstitutes TCR-inducted phospholipase Cγ1 phosphorylation, extracellular signal–regulated kinase activation, and nuclear factor of activated T cells (NFAT) promoter activity in LAT-deficient Jurkat T cells (J.CaM2). Mutation of the chimeric construct precluding its recruitment to GEMs diminishes but does not eliminate its ability to support TCR signaling. Expression of a chimera that lacks SLP-76 amino acids 224–244 restores NFAT promoter activity, suggesting that if localized, SLP-76 does not require an association with Gads to promote T cell activation. In contrast, mutation of the protein tyrosine kinase phosphorylation sites of SLP-76 in the context of the LAT/SLP-76 chimera abolishes reconstitution of TCR function. Collectively, these experiments show that optimal TCR signaling relies on the compartmentalization of SLP-76 and that one critical function of LAT is to bring SLP-76 and its associated proteins to the membrane

Foliar application of microdoses of sucrose to reduce codling moth Cydia pomonella L. (Lepidoptera: Tortricidae) damage to apple trees

Abstract BACKGROUND The effects of foliar applications of microdoses of sucrose to reduce the damage by the codling moth have been reported from nine trials carried in France and Algeria from 2009 to 2014. The activity of sucrose alone was assessed by comparison with an untreated control and some treatments with the Cydia pomonella granulovirus or a chemical insecticide. The addition of sucrose to these different treatments was also investigated. RESULTS The application of sucrose at 0.01% reduced the means of infested fruits with a value of Abbott's efficacy of 41.0 ± 10.0%. This involved the induction of resistance by antixenosis to insect egg laying. Indeed, it seems that acceptance of egg laying on leaves treated with sucrose was reduced. The addition of sucrose to thiacloprid improved its efficacy (59.5% ± 12.8) by 18.4%. However, the sucrose had no added value when associated with C. pomonella granulovirus treatments. CONCLUSION Foliar applications of microdoses of sucrose every 20 days in commercial orchards can partially protect against the codling moth. Its addition to thiacloprid increases the efficacy in integrated control strategies, contrary to C. pomonella granulovirus treatments. This work opens a route for the development of new biocontrol strategies

Sparsity enables estimation of both subcortical and cortical activity from MEG and EEG

Subcortical structures play a critical role in brain function. However, options for assessing electrophysiological activity in these structures are limited. Electromagnetic fields generated by neuronal activity in subcortical structures can be recorded noninvasively, using magnetoencephalography (MEG) and electroencephalography (EEG). However, these subcortical signals are much weaker than those generated by cortical activity. In addition, we show here that it is difficult to resolve subcortical sources because distributed cortical activity can explain the MEG and EEG patterns generated by deep sources. We then demonstrate that if the cortical activity is spatially sparse, both cortical and subcortical sources can be resolved with M/EEG. Building on this insight, we develop a hierarchical sparse inverse solution for M/EEG. We assess the performance of this algorithm on realistic simulations and auditory evoked response data, and show that thalamic and brainstem sources can be correctly estimated in the presence of cortical activity. Our work provides alternative perspectives and tools for characterizing electrophysiological activity in subcortical structures in the human brain