Basal intercellular junctions integrate local cytoskeletal forces to regulate Hippo signalling in growing epithelia
Authors: Benjamin Kroeger 1; Samuel Manning 1; Yoshana Fonseka 1; Kieran Harvey 1,2
Affiliations: 1) Monash Biomedical Discovery Institute, Monash University, Melbourne, Australia; 2) Peter MacCallum Cancer Centre, Melbourne, Australia
Keywords: t. cell junctions and adhesion; w. Hippo signaling
The Hippo signalling pathway is an evolutionarily conserved regulator of organ growth and homeostasis. By the assembly of pathway components in discrete subcellular domains, Hippo signalling can be either amplified or attenuated. The main subdomains previously associated with Hippo signalling in fly tissues are found at the apical portion of epithelial cells, and include the adherens junctions and apical membranes. Hippo signalling can be modulated by cytoskeletal tension, which exerts forces at the adherens junctions and influences the subcellular localisation of the key Hippo pathway kinase, Warts.
Using a combination of molecular genetic approaches and high-resolution imaging, we discovered a novel subcellular domain where Warts is enriched: punctate, basal intercellular junctions. Using APEX2 transmission electron microscopy we found that in addition to its known enrichment at apical junctions, Warts accumulates in focal intercellular junctions at the basal-most region of epithelial tissues. Our genetic analyses show that the basal junctions are similar in composition to the belt-like adherens junctions. We reveal that Warts is dynamically recruited by LIM-family proteins to punctate basal junctions in response to local cytoskeletal forces, driven by myosin activity. By recruiting Warts basally, it is spatially restricted from activators of Hippo pathway signalling, which are enriched at the apical portion of epithelial cells. Our study sheds light on how the Hippo pathway integrates mechanical signals, and highlights previously overlooked aspects of cell biology and tissue dynamics that operate at the basal region of growing epithelial tissues.