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 journalArticlepeer-review


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
Issue number3
StatePublished - Mar 2007
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization'. Together they form a unique fingerprint.

Cite this