The Spectrin cytoskeleton regulates the Hippo signalling pathway

Abstract

The Spectrin cytoskeleton is known to be polarised in epithelial cells, yet its role remains poorly understood. Here, we show that the Spectrin cytoskeleton controls Hippo signalling. In the developing Drosophila wing and eye, loss of apical Spectrins (alpha/beta‐heavy dimers) produces tissue overgrowth and mis‐regulation of Hippo target genes, similar to loss of Crumbs (Crb) or the FERM‐domain protein Expanded (Ex). Apical beta‐heavy Spectrin binds to Ex and co‐localises with it at the apical membrane to antagonise Yki activity. Interestingly, in both the ovarian follicular epithelium and intestinal epithelium of Drosophila, apical Spectrins and Crb are dispensable for repression of Yki, while basolateral Spectrins (alpha/beta dimers) are essential. Finally, the Spectrin cytoskeleton is required to regulate the localisation of the Hippo pathway effector YAP in response to cell density human epithelial cells. Our findings identify both apical and basolateral Spectrins as regulators of Hippo signalling and suggest Spectrins as potential mechanosensors. In Drosophila, both the apical and the basolateral Spectrin cytoskeleton are able to activate the Hippo signaling pathway in a tissue‐dependent manner. In cultured human cells this depends on cell density, suggesting a role for Spectrins in mechanosensing. In Drosophila, both the apical and the basolateral Spectrin cytoskeleton are able to activate the Hippo signaling pathway in a tissue‐dependent manner. In cultured human cells this depends on cell density, suggesting a role for Spectrins in mechanosensing.

Cited by papers we hold 6

• The Hippo Signaling Pathway: The Trader of Tumor Microenvironment · 2021
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• Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression · 2021
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• The Hippo pathway integrates PI3K–Akt signals with mechanical and polarity cues to control tissue growth · 2019
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• Role of Hippo Pathway-YAP/TAZ Signaling in Angiogenesis · 2019
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• Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation · 2016
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• Integrin signalling regulates YAP/TAZ to control skin homeostasis · 2016
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