Tension-dependent regulation of mammalian Hippo signaling through LIMD1

Author:

Ibar Consuelo1,Kirichenko Elmira1,Keepers Benjamin1ORCID,Enners Edward1,Fleisch Katelyn1,Irvine Kenneth D.1ORCID

Affiliation:

1. Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway NJ 08854 USA

Abstract

Hippo 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.

Funder

Office of Extramural Research, National Institutes of Health

NJCCR

Publisher

The Company of Biologists

Subject

Cell Biology

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