scholarly journals Tension-dependent regulation of mammalian Hippo signaling through LIMD1

2017 ◽  
Author(s):  
Consuelo Ibar ◽  
Elmira Kirichenko ◽  
Benjamin Keepers ◽  
Edward Enners ◽  
Katelyn Fleisch ◽  
...  

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.






Author(s):  
M. Dilani Senadheera ◽  
Celine Levesque ◽  
Dennis G. Cvitkovitch


Cell ◽  
2014 ◽  
Vol 156 (5) ◽  
pp. 893-906 ◽  
Author(s):  
Masaki Mori ◽  
Robinson Triboulet ◽  
Morvarid Mohseni ◽  
Karin Schlegelmilch ◽  
Kriti Shrestha ◽  
...  






2002 ◽  
Vol 365 (2) ◽  
pp. 513-519 ◽  
Author(s):  
Javelle R. SYMONS ◽  
Charles M. LeVEA ◽  
Robert A. MOONEY

The leucocyte common antigen-related phosphatase (LAR) has been implicated in receptor tyrosine kinase signalling pathways while also displaying cell-density-dependency and localization to adherens junctions. Whereas physiological substrates for LAR have not been identified unequivocally, β-catenin associates with LAR and is a substrate in vitro. With the implication that LAR may play a role in regulating E-cadherin-dependent cell—cell communication and contact inhibition, the relationship of LAR with E-cadherin was investigated. LAR expression increased with cell density in the human breast cancer cell line MCF-7 and in Ln 3 cells derived from the 13762NF rat mammary adenocarcinoma. LAR protein levels decreased rapidly when cells were replated at a low density after attaining high expression of LAR at high cell density. COS-7 cells displayed comparable density-dependent regulation of LAR expression when transiently expressing exogenous LAR under the control of a constitutively active promoter, indicating that the regulation of expression is not at the level of gene regulation. Disrupting homophilic E-cadherin complexes by chelating extracellular calcium caused a marked decrease in LAR protein levels. Similarly, blocking E-cadherin interactions with saturating amounts of E-cadherin antibody (HECD-1) also led to a rapid and pronounced loss of cellular LAR. In contrast, mimicking cell-surface E-cadherin engagement by plating cells at low density on to dishes coated with HECD-1 resulted in a 2-fold increase in LAR expression compared with controls. These results suggest that density-dependent regulation of LAR expression is mediated by functional E-cadherin and may play a role in density-dependent contact inhibition by regulating tyrosine phosphorylation in E-cadherin complexes.



2015 ◽  
Author(s):  
Sarangam Majumdar ◽  
Subhoshmita Mondal

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.



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