Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization |
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Authors: | Li Juying Brieher William M Scimone M Lucila Kang Shin Jung Zhu Hong Yin Helen von Andrian Ulrich H Mitchison Timothy Yuan Junying |
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Institution: | Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA. |
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Abstract: | Coordinated regulation of cell migration, cytokine maturation and apoptosis is critical in inflammatory responses. Caspases, a family of cysteine proteases, are known to regulate cytokine maturation and apoptosis. Here, we show that caspase-11, a mammalian pro-inflammatory caspase, regulates cell migration during inflammation. Caspase-11-deficient lymphocytes exhibit a cell-autonomous migration defect in vitro and in vivo. We demonstrate that caspase-11 interacts physically and functionally with actin interacting protein 1 (Aip1), an activator of cofilin-mediated actin depolymerization. The caspase-recruitment domain (CARD) of caspase-11 interacts with the carboxy-terminal WD40 propeller domain of Aip1 to promote cofilin-mediated actin depolymerization. Cells with Aip1 or caspase-11 deficiency exhibit defects in actin dynamics. Using in vitro actin depolymerization assays, we found that caspase-11 and Aip1 work cooperatively to promote cofilin-mediated actin depolymerization. These data demonstrate a novel cell autonomous caspase-mediated mechanism that regulates actin dynamics and mammalian cell migration distinct from the receptor mediated Rho-Rac-Cdc42 pathway. |
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