Author response: Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription [peer_review]

Sherzod A Tokamov, Ting Su, Anne Ullyot, Richard G Fehon
2020 unpublished
The Hippo (Hpo) pathway regulates tissue growth in many animals. Multiple upstream components promote Hpo pathway activity, but the organization of these different inputs, the degree of crosstalk between them, and whether they are regulated in a distinct manner is not well understood. Kibra (Kib) activates the Hpo pathway by recruiting the core Hpo kinase cassette to the apical cortex. Here, we show that the Hpo pathway downregulates Drosophila Kib levels independently of Yorkie-mediated
more » ... iption. We find that Hpo signaling complex formation promotes Kib degradation via SCF Slimb -mediated ubiquitination, that this effect requires Merlin, Salvador, Hpo, and Warts, and that this mechanism functions independently of other upstream Hpo pathway activators. Moreover, Kib degradation appears patterned by differences in mechanical tension across the wing. We propose that Kib degradation mediated by Hpo pathway components and regulated by cytoskeletal tension serves to control Kib-driven Hpo pathway activation and ensure optimally scaled and patterned tissue growth. Tokamov et al. eLife 2021;10:e62326.
doi:10.7554/elife.62326.sa2 fatcat:bf2lhxcf3fbu7lhz3heb3qyyuu