Tension-dependent regulation of mammalian Hippo signaling through LIMD1

ABSTRACTHippo signaling is regulated by biochemical and biomechanical cues that influence the cytoskeleton, but the mechanisms that mediate this have remained unclear. We show that all three mammalian Ajuba family proteins – AJUBA, LIMD1, and WTIP - exhibit tension-dependent localization to adherens junctions, and that both Lats family proteins, LATS1 and LATS2, exhibit an overlapping tension-dependent junctional localization. This localization of Ajuba and Lats family proteins is also influenced by cell density, and by Rho activation. We establish that junctional localization of Lats kinases requires LIMD1, and that LIMD1 is also specifically required for the regulation of Lats kinases and YAP by Rho. Our results identify a biomechanical pathway that contributes to regulation of mammalian Hippo signaling, establish that this occurs through tension-dependent LIMD1-mediated recruitment and inhibition of Lats kinases in junctional complexes, and identify roles for this pathway in both Rho-mediated and density-dependent regulation of Hippo signaling.

Perspectives on Quorum sensing in Fungi

Keeping a pace with Quorum sensing, analyzing communication shows the close co-evolution of fungi with organisms present in their environment giving insights into multispecies communication. Subsequently, many examples of cell density dependent regulation by extracellular factors have been found in diverse microorganisms. The widespread incidence of diverse quorum-sensing systems strongly suggests that regulation in accordance with cell density is important for the success of microbes in many environments. The paper includes the basic autoregulatory quorum sensing molecules that has been perceived. Although fungal quorum sensing research is still in its infancy, its discovery has changed our views about the fungal kingdom and could eventually lead to the development of new antifungal therapeutics.