Article abstract
Nature Cell Biology 9, 276 - 286 (2007)
Published online: 11 February 2007 | doi:10.1038/ncb1541
There is an Addendum (April 2007) associated with this Article.
Caspase-11 regulates cell migration by promoting Aip1–Cofilin-mediated actin depolymerization
Juying Li1, William M. Brieher2, M. Lucila Scimone3, Shin Jung Kang1,5, Hong Zhu1, Helen Yin4, Ulrich H. von Andrian3, Timothy Mitchison2 & Junying Yuan1
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.
- Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
- Department of Systems Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
- The CBR Institute for Biomedical Research, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA.
- Department of Physiology, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
- Current address: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.
Correspondence to: Junying Yuan1 e-mail: jyuan@hms.harvard.edu
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