Chemico-genetic identification of drebrin as a regulator of calcium responses |
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Authors: | Jason C Mercer Qian Qi Laurie F Mottram Mankit Law Danny Bruce Archana Iyer J Luis Morales Hiroyuki Yamazaki Tomoaki Shirao Blake R Peterson Avery August |
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Institution: | 1. Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth, Military Medical University, Xi''an, Shaanxi 710032, China;2. Department of Neurosurgery, The 123th Hospital of PLA, Bengbu, Anhui 233000, China |
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Abstract: | Store-operated calcium channels are plasma membrane Ca2+ channels that are activated by depletion of intracellular Ca2+ stores, resulting in an increase in intracellular Ca2+ concentration, which is maintained for prolonged periods in some cell types. Increases in intracellular Ca2+ concentration serve as signals that activate a number of cellular processes, however, little is known about the regulation of these channels. We have characterized the immuno-suppressant compound BTP, which blocks store-operated channel mediated calcium influx into cells. Using an affinity purification scheme to identify potential targets of BTP, we identified the actin reorganizing protein, drebrin, and demonstrated that loss of drebrin protein expression prevents store-operated channel mediated Ca2+ entry, similar to BTP treatment. BTP also blocks actin rearrangements induced by drebrin. While actin cytoskeletal reorganization has been implicated in store-operated calcium channel regulation, little is known about actin-binding proteins that are involved in this process, or how actin regulates channel function. The identification of drebrin as a mediator of this process should provide new insight into the interaction between actin rearrangement and store-operated channel mediated calcium influx. |
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