Abstract
T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate. The absence of coronin-1, although it did not affect T cell development, resulted in a profound defect in Ca2+ mobilization, interleukin-2 production, T cell proliferation and T cell survival. We conclude that coronin-1, through activation of Ca2+ release from intracellular stores, is an essential regulator of peripheral lymphocyte survival.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Animals
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Calcium / metabolism*
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Calcium Signaling / genetics
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Calcium Signaling / physiology
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Cell Survival / genetics
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Cell Survival / immunology
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Inositol 1,4,5-Trisphosphate / biosynthesis*
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Intracellular Fluid / immunology
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Intracellular Fluid / metabolism
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Microfilament Proteins / deficiency
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Microfilament Proteins / genetics
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Microfilament Proteins / physiology*
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell / physiology
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Type C Phospholipases / metabolism
Substances
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Actins
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Microfilament Proteins
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Receptors, Antigen, T-Cell
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coronin proteins
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Inositol 1,4,5-Trisphosphate
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Type C Phospholipases
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Calcium