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author:("mat1a, Didi")
1.  Emerging Roles of L-Type Voltage-Gated and Other Calcium Channels in T Lymphocytes 
In T lymphocytes, calcium ion controls a variety of biological processes including development, survival, proliferation, and effector functions. These distinct and specific roles are regulated by different calcium signals, which are generated by various plasma membrane calcium channels. The repertoire of calcium-conducting proteins in T lymphocytes includes store-operated CRAC channels, transient receptor potential channels, P2X channels, and L-type voltage-gated calcium (Cav1) channels. In this paper, we will focus mainly on the role of the Cav1 channels found expressed by T lymphocytes, where these channels appear to operate in a T cell receptor stimulation-dependent and voltage sensor independent manner. We will review their expression profile at various differentiation stages of CD4 and CD8 T lymphocytes. Then, we will present crucial genetic evidence in favor of a role of these Cav1 channels and related regulatory proteins in both CD4 and CD8 T cell functions such as proliferation, survival, cytokine production, and cytolysis. Finally, we will provide evidence and speculate on how these voltage-gated channels might function in the T lymphocyte, a non-excitable cell.
PMCID: PMC3757574  PMID: 24009608
Cav1 channels; calcium channels; CD4 T cells; CD8 T cells; CRAC channel
2.  A scaffold protein, AHNAK1 is required for calcium signalling during T cell activation 
Immunity  2008;28(1):64-74.
Engagement of the T cell antigen receptor (TCR) during antigen presentation initiates a coordinated action of a large number of signaling proteins and ion channels. AHNAK1 is a scaffold protein, highly expressed novel and a critical component for calcium signalling during CD4 T cell activation. We show that AHNAK1−/− mice are highly susceptible to Leishmania major infection. We found that AHNAK1−/− CD4 T cells respond poorly to TCR stimulation in vitro with low proliferation and low IL-2 production. Furthermore, AHNAK1 deficiency results in a reduced calcium influx upon TCR cross-linking and subsequent poor NFAT activation. We found that AHNAK1 is required for plasma membrane expression of L-type calcium channels α1S (Cav1.1) probably through its interaction with the β regulatory subunit.
PMCID: PMC2350190  PMID: 18191595
3.  Invariant Chain Controls H2-M Proteolysis in Mouse Splenocytes and Dendritic Cells 
The Journal of Experimental Medicine  2000;191(6):1057-1062.
The association of invariant (Ii) chain with major histocompatibility complex (MHC) class II dimers is required for proper antigen presentation to T cells by antigen-presenting cells. Mice lacking Ii chain have severe abnormalities in class II transport, T cell selection, and B cell maturation. We demonstrate here that H2-M, which is required for efficient class II antigenic peptide loading, is unexpectedly downregulated in splenocytes and mature dendritic cells (DCs) from Ii−/− mice. Downregulation reflects an increased rate of degradation in Ii−/− cells. Degradation apparently occurs within lysosomes, as it is prevented by cysteine protease inhibitors such as E64, but not by the proteasome inhibitor lactacystin. Thus, Ii chain may act as a lysosomal protease inhibitor in B cells and DCs, with its deletion contributing indirectly to the loss of H2-M.
PMCID: PMC2193111  PMID: 10727467
invariant chain; H2-M; DM; cathepsin; dendritic cell

Results 1-3 (3)