RRC ID 36310
Author Liu B, Zheng Y, Yin F, Yu J, Silverman N, Pan D.
Title Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila.
Journal Cell
Abstract 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.
Volume 164(3)
Pages 406-19
Published 2016-1-28
DOI 10.1016/j.cell.2015.12.029
PII S0092-8674(15)01693-1
PMID 26824654
PMC PMC4733248
MeSH Animals DNA-Binding Proteins / metabolism Drosophila Proteins / metabolism Drosophila melanogaster / growth & development Drosophila melanogaster / immunology* Drosophila melanogaster / metabolism Drosophila melanogaster / microbiology Escherichia coli / physiology Fat Body / metabolism Immunity, Innate* Intracellular Signaling Peptides and Proteins / metabolism Larva / metabolism Male Pectobacterium carotovorum / physiology Phosphoproteins / metabolism Protein Serine-Threonine Kinases / metabolism Signal Transduction* Staphylococcus aureus / physiology Toll-Like Receptors / metabolism
IF 38.637
Times Cited 101
Drosophila DGRC#103070