CYTOSKELETON IKK and Caspases in Regulating Cell Shape

Two reports this week provide evidence that in Drosophila IKK, a kinase of the IKK family, which stands for inhibitor of nuclear factor B (NF-B) kinase, promotes the degradation of DIAP1, the Drosophila inhibitor of apoptosis protein, and activates the DRONC caspase to regulate nonapoptotic processes. Kuranaga et al. found mutant forms of IKK lacking kinase activity in a screen for suppressors of cell death. Although overexpression of IKK did promote cell death, knockdown of IKK did not suppress cell death, suggesting that the IKK may have a nonapoptotic function. IKK promoted the phosphorylation of DIAP1 and the degradation of DIAP1 in S2 cells. Although the two proteins coimmunoprecipitated from S2 cells, purified proteins did not physically interact, suggesting that the interaction may be indirect. In wing discs, mild caspase activation was detected in the absence of apoptosis, and this caspase activation was inhibited when IKK was knocked down. Oshima et al. showed that overexpression of IKK disrupted epithelial integrity in the Drosophila embryo tracheal system, and this was associated with a loss of apical F actin and loss of cell polarity in the epithelial cells. In S2 cells, altering the abundance of IKK altered cell morphology, with decreased IKK stimulating the frequency of serrate- or stellate-shaped cells and decreasing retrograde F actin flow and increased IKK stimulating membrane ruffling and increasing retrograde F actin flow. In the trachea, sensory bristles, and antenna arista, inhibition of IKK promoted excessive branching of the structures, which was consistent with disruption in actin regulation. Genetic interactions were observed in the arista phenotype between IKK, DIAP1, and DRONC, suggesting that IKK regulates the F actin cytoskeleton by stimulating caspase activity. Thus, these two results uncover a novel activation of caspases through an IKK and a nonapoptotic function for caspases in regulating the actin cytoskeleton. (Bergmann and Montell discuss the implications of these findings.)

E. Kuranaga, H. Kanuka, A. Tonoki, K. Takemoto, T. Tomioka, M. Kobayashi, S. Hayashi, M. Miura, Drosophila IKK-related kinase regulates nonapoptotic function of caspases via degradation of IAPs. Cell 126, 583-596 (2006). [PubMed]

K. Oshima, M. Takeda, E. Kuranaga, R. Ueda, T. Aigaki, M. Miura, S. Hayashi, IKK regulates F actin assembly and interacts with Drosophila IAP1 in cellular morphogenesis. Curr. Biol. 16, 1531-1537 (2006). [PubMed]

A. Bergmann, IKK signaling: Not just NF-B. Curr. Biol. 16, R588-R590 (2006). [PubMed]

D. J. Montell, A kinase gets caspases into shape. Cell 126, 450-452 (2006). [PubMed]

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PERSPECTIVES
STKE Perspectives
Migrate, Differentiate, Proliferate, or Die: Pleiotropic Functions of an Apical "Apoptotic Caspase"

Sharad Kumar (12 October 2004)
Sci. STKE 2004 (254), pe49. [DOI: 10.1126/stke.2542004pe49]
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