Caspase-11 regulates cell migration by promoting Aip1–Cofilin-mediated actin depolymerization
J Li, WM Brieher, ML Scimone, SJ Kang, H Zhu… - Nature cell …, 2007 - nature.com
Nature cell biology, 2007•nature.com
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) …
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) …
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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