Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization

Juying Li, William M. Brieher, M. Lucila Scimone, Shin Jung Kang, Hong Zhu, Helen Yin, Ulrich H. von Andrian, Timothy Mitchison, Junying Yuan

Research output: Contribution to journalArticle

89 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)276-286
Number of pages11
JournalNature cell biology
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Cell Biology

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    Li, J., Brieher, W. M., Scimone, M. L., Kang, S. J., Zhu, H., Yin, H., von Andrian, U. H., Mitchison, T., & Yuan, J. (2007). Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization. Nature cell biology, 9(3), 276-286. https://doi.org/10.1038/ncb1541