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Available from: James J Chou, Sep 23, 2015
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    • "Second, as posited by the Safety TCR triggering model, due to its negatively charged lipid composition, these microdomains could provide a suitable environment for the sequestration of intracellular chains of CD3ζ and CD3ε via the interaction of its basic residue-rich sequences with the inner leaflet of the PM, thus preventing them from being targeted by active Lck (Kuhns and Davis, 2008; Xu et al., 2008). Despite the fact that the mechanism liberating these CD3 chains from the PM (Fernandes et al., 2010; Gagnon et al., 2010) as well as the lipid composition of heavy DRMs have not been elucidated, coupling the presence of CD45 with the “Safety TCR Trigger” mechanism endows these domains with a powerful anti-pY mechanism to maintain a non-signaling phenotype in resting T cells. Moreover, it is quite likely that adaptor proteins PAG and LAT reside in a slightly distinct type of membrane microdomains, as their profile of Brij58 solubilization pattern is only partially overlapping (Brdicka et al., 2000). "
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    ABSTRACT: In spite of a comprehensive understanding of the schematics of T cell receptor (TCR) signaling, the mechanisms regulating compartmentalization of signaling molecules, their transient interactions, and rearrangement of membrane structures initiated upon TCR engagement remain an outstanding problem. These gaps in our knowledge are exemplified by recent data demonstrating that TCR triggering is largely dependent on a preactivated pool of Lck concentrated in T cells in a specific type of membrane microdomains. Our current model posits that in resting T cells all critical components of TCR triggering machinery including TCR/CD3, Lck, Fyn, CD45, PAG, and LAT are associated with distinct types of lipid-based microdomains which represent the smallest structural and functional units of membrane confinement able to negatively control enzymatic activities and substrate availability that is required for the initiation of TCR signaling. In addition, the microdomains based segregation spatially limits the interaction of components of TCR triggering machinery prior to the onset of TCR signaling and allows their rapid communication and signal amplification after TCR engagement, via the process of their coalescence. Microdomains mediated compartmentalization thus represents an essential membrane organizing principle in resting T cells. The integration of these structural and functional aspects of signaling into a unified model of TCR triggering will require a deeper understanding of membrane biology, novel interdisciplinary approaches and the generation of specific reagents. We believe that the fully integrated model of TCR signaling must be based on membrane structural network which provides a proper environment for regulatory processes controlling TCR triggering.
    Full-text · Article · Jun 2012 · Frontiers in Immunology
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    • "It was proposed that this interaction represents a safety switch to avoid erroneous TCR/CD3 tyrosine phosphorylation under resting T cell conditions (Kuhns and Davis, 2008). This proposal was subject to discussion following reports that tyrosine phosphorylation of CD3ε cytoplasmic domain did not increase when these basic residues were mutated (Fernandes et al., 2010; Gagnon et al., 2010). A role of PS in generation of signaling protein membrane networks at TCR triggering sites was suggested by reconstructing LATanchored TCR lipid/signaling protein network in vitro: tyrosine phosphorylated LAT was recombinantly expressed as membraneanchored variant in insect cells and inserted into liposomes. "

    Full-text · Article · Mar 2012 · Frontiers in Immunology
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    ABSTRACT: This paper presents a low-power design and an area-efficient FPGA implementation of digital channel selection filtering processor for radio receiver. For an homodyne wide-band RF receiver and sigma-delta modulator, two filtering cascade structures composed of 5 stages comb filter, FIR half-band filter and selector filter are compared. Design flow of hardware architecture is presented through digital data format representation and topology of digital operators. Experimental results are given to evaluate performances and complexity of designed FPGA-based implementation.
    No preview · Conference Paper · Jan 2005
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