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Buiter, S.

Publications and source records attributed to Buiter, S..

2 recordsLinked to original sources

Cortical tension regulates Hippo signaling via Par-1-mediated Kibra degradation

The Hippo pathway is an evolutionarily conserved regulator of tissue growth. Multiple Hippo signaling components are regulated via proteolytic degradation. However, how these degradation mechanisms are themselves modulated remains unexplored. Kibra is a key upstream pathway activator that promotes its own ubiquitin-mediated degradation upon assembling a Hippo signaling complex. Here, we demonstrate that Hippo complex-dependent Kibra degradation is modulated by cortical tension. Using classical genetic, osmotic, and pharmacological manipulations of myosin activity and cortical tension, we show that increasing cortical tension leads to Kibra degradation, whereas decreasing cortical tension increases Kibra abundance. Our study also implicates Par-1 in regulating Kib abundance downstream of cortical tension. We demonstrate that Par-1 promotes ubiquitin-mediated Kib degradation in a Hippo complex-dependent manner and is required for tension-induced Kib degradation. Collectively, our results reveal a previously unknown molecular mechanism by which cortical tension affects Hippo signaling and provide novel insights into the role of mechanical forces in growth control.

cell biology↗

Apical polarity and actomyosin dynamics regulate Hippo signaling by controlling Kibra subcellular localization

Cell polarity and actomyosin networks are key features that organize cells of epithelial tissues and are known to regulate tissue growth. However, the mechanisms by which polarity cues and actomyosin cytoskeleton influence intracellular signaling cascades that control growth remain poorly understood. The Hippo pathway is an evolutionarily conserved regulator of tissue growth and is known to integrate inputs from both polarity and actomyosin components. An upstream activator of the Hippo pathway, Kibra, localizes into distinct pools at the junctional and medial regions of the apical cortex in epithelial cells, and medial accumulation was shown to promote Kibra activity. Here, we demonstrate that cortical Kibra distribution is controlled by a tug of war between apical polarity and actomyosin dynamics. We show that while the apical polarity network, in part via aPKC, tethers Kibra at the junctional cortex to silence its activity, medial actomyosin flows promote Kibra-mediated Hippo complex formation at the medial cortex, thereby activating the Hippo pathway. This study provides a mechanistic understanding of the relationship between the Hippo pathway, polarity, and actomyosin cytoskeleton and offers novel insights into how fundamental features of epithelial tissue architecture can serve as inputs into signaling cascades that control tissue growth, patterning, and morphogenesis.

cell biology↗