title: 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.
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK - London Research Institute, London, UK.
authors.forename: Georgina C
authors.initials: GC
authors.lastname: Fletcher
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK - London Research Institute, London, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elbediwy
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK - London Research Institute, London, UK.
authors.forename: Ichha
authors.initials: I
authors.lastname: Khanal
authors.affiliation: Apoptosis and Cell Proliferation Laboratory, Cancer Research UK - London Research Institute, London, UK Barts Cancer Institute, Queen Mary University of London, London, UK.
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Ribeiro
authors.affiliation: Apoptosis and Cell Proliferation Laboratory, Cancer Research UK - London Research Institute, London, UK nic.tapon@cancer.org.uk barry.thompson@cancer.org.uk.
authors.forename: Nic
authors.initials: N
authors.lastname: Tapon
authors.affiliation: Epithelial Biology Laboratory, Cancer Research UK - London Research Institute, London, UK nic.tapon@cancer.org.uk barry.thompson@cancer.org.uk.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Thompson
mesh_terms: D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013049:Spectrin / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D013049:Spectrin; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C064360:crb protein, Drosophila; C085090:ex protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Hippo signalling; Spectrin; YAP; cytoskeleton