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Differential calcium signaling and Kv1.3 trafficking to the immunological synapse in systemic lupus erythematosus
Author(s) -
Nicolaou Stella A,
Neumeier Lisa,
Lee Susan Molleran,
Ragupathy Manoj,
Duncan Heather J,
Kant Shashi K,
Mongey Anne Barbara,
Filipovich Alexandra H,
Conforti Laura
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1181.15
Subject(s) - immunological synapse , homeostasis , microbiology and biotechnology , immunology , calcium signaling , t cell , chemistry , signal transduction , biology , t cell receptor , immune system
Systemic lupus erythematosus (SLE) T cells have several activation signaling anomalies including defective Ca2+ response and increased NF‐AT nuclear translocation. The duration of the Ca2+ signal is critical in the activation of specific transcription factors and a sustained Ca2+ response activates NF‐AT. Yet, the distribution of Ca2+ responses in SLE T cells is not known. Furthermore, the mechanisms responsible for Ca2+ alterations are not fully understood. Kv1.3 channels control Ca2+ homeostasis in T cells. We reported a defect in Kv1.3 trafficking to the immunological synapse (IS) of SLE T cells that might contribute to the Ca2+ defect. Here, we compared single T cell quantitative Ca2+ responses upon formation of the IS in SLE, normal and rheumatoid arthritis (RA) donors. Also, we correlated cytosolic Ca2+ and Kv1.3 trafficking in the IS by two‐photon microscopy. We found that sustained Ca2+ responses are prevalent in SLE, but not in normal and RA T cells. The ratio of sustained over transient responses in SLE T cells was 3‐fold that of normal and RA T cells. Further, we observed that in normal T cells termination of Ca2+ influx is accompanied by Kv1.3 permanence in the IS, while Kv1.3 premature exit from the IS correlates with sustained Ca2+ responses in SLE T cells. Thus, we propose that the altered distribution in Ca2+ signaling in SLE T cells depends on the Kv1.3 channel trafficking defect. (NIH CA95286 and AHA 0615213B)