PP2A phosphatase regulates Hippo signalling in dual manner

Area of Science:

• Cell Biology
• Developmental Biology
• Molecular Biology

Background:

• Hippo signaling is crucial for regulating tissue growth and is influenced by cellular polarity.
• The FERM domain protein Expanded (Ex) activates Hippo signaling by integrating polarity cues.
• The apicobasal polarity protein Crumbs limits Hippo activity by promoting Ex phosphorylation and degradation.

Purpose of the Study:

• To investigate the role of protein phosphatase 2A (PP2A) in regulating Hippo signaling.
• To elucidate the dual functions of PP2A in Drosophila melanogaster cell culture and wing discs.
• To understand how PP2A interacts with polarity cues and the Expanded (Ex) protein.

Main Methods:

• Utilized Drosophila cell culture and wing disc models.
• Investigated the effects of different PP2A holoenzymes (PP2A^Wrd, PP2A^Cka, PP2A^Tws) on Hippo signaling components.
• Examined the interaction between PP2A, Expanded (Ex), Crumbs, and Kibra.

Main Results:

• PP2A^Wrd dephosphorylates and stabilizes Ex, counteracting Crumbs-mediated degradation and activating Hippo signaling.
• PP2A^Wrd holoenzyme increases Hippo signaling activity, contrasting with the inhibitory role of PP2A^Cka-containing STRIPAK complex.
• Kibra interacts with PP2A^Wrd to prevent Ex degradation but cannot antagonize Crumbs-mediated Ex regulation.

Conclusions:

• PP2A plays a novel, Hippo-activating role in stabilizing Ex, crucial for tissue growth control.
• PP2A tightly regulates Hippo activity in response to cellular polarity stimuli.
• This study provides new insights into the intricate mechanisms controlling Hippo signaling.