Targeting of calcium:calmodulin signals to the cytoskeleton by IQGAP1 |
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Authors: | Psatha Maria I Razi Minoo Koffer Anna Moss Steve E Sacks David B Bolsover Stephen R |
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Institution: | Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States. |
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Abstract: | Mast cells reorganize their actin cytoskeleton in response to cytosolic calcium signals while in parallel secreting histamine and other inflammatory mediators. The effect of calcium on actin is mediated in large part through calmodulin. EGFP-tagged calmodulin is concentrated in the actin-rich cortex of RBL-2H3 mast cells. Transfection with small interfering RNA directed against the actin and calmodulin-binding protein IQGAP1 dramatically reduced expression of the latter protein and reduced or eliminated the concentration of calmodulin at the actin-rich cortex. Both actin reorganization and secretion were enhanced in IQGAP1 knockdown cells. Our results suggest a model in which calmodulin is targeted to and sequestered at the actin cytoskeleton by IQGAP1. Upon cell stimulation and the subsequent Ca2+]i increase, it is immediately available to activate local downstream targets. |
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Keywords: | Calmodulin IQGAP1 Mast cell RBL-2H3 Actin Calcium |
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