Hippo in innate immunity

Toll receptor-mediated Hippo signaling controls innate immunity in Drosophila.  Cell 164: 406–419.

The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innate immunity whereby Yorkie directly regulates the transcription of the Drosophila IκB homolog, Cactus, in Toll receptor-mediated antimicrobial response. Loss of Hippo pathway tumor suppressors or activation of Yorkie in fat bodies, the Drosophila immune organ, leads to elevated cactus mRNA levels, decreased expression of antimicrobial peptides, and vulnerability to infection by Gram-positive bacteria. Furthermore, Gram-positive bacteria acutely activate Hippo-Yorkie signaling in fat bodies via the Toll-Myd88-Pelle cascade through Pelle-mediated phosphorylation and degradation of the Cka subunit of the Hippo-inhibitory STRIPAK PP2A complex. Our studies elucidate a Toll-mediated Hippo signaling pathway in antimicrobial response, highlight the importance of regulating IκB/Cactus transcription in innate immunity, and identify Gram-positive bacteria as extracellular stimuli of Hippo signaling under physiological settings.

Dr. DJPラボから、Hippo pathwayの新たな展開。Drosophilaのinnate immune responseにおいて、Hippo-Yki signalingがCactus（IκB homolog）のtranscriptional regulationに関与しているという話。Toll receptorの下で、Pll-mediated phosphorylationとCka degradationを介してHpoがactivateされる。うむ、キレイにcell autonomousにきとるね。Hippoってほんまに色んなところに関与しとるなぁ。ほいで、やっぱりDJPはすごいな。。。

"It is interesting to note that organ size control and innate immunity are two ancient features of metazoans. Our findings that the signaling pathways underlying these seemingly disparate processes (Hippo and Toll) are functionally intertwined may therefore have a deep evolutionary origin. Interestingly, Toll receptor and Hippo signaling have both been implicated in other biological processes such as cell competition in the wing disc and polarized cell rearrangements in Drosophila embryos, although their molecular relationship in these processes has not been determined."

"We further speculate that such a link may potentially contribute to the oncogenic activity of YAP/TAZ, whereby YAP/TAZ may protect the tumor cells from immune attack through the induction of IκB expression and inhibition of inflammation."

そうそう、こういうことね。ナイス。