Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth

English version

Autoři: Ritu Sarpal ^aff001; Victoria Yan ^aff001; Lidia Kazakova ^aff001; Luka Sheppard ^aff001; Jessica C. Yu ^aff002; Rodrigo Fernandez-Gonzalez ^aff001; Ulrich Tepass ^aff001
Působiště autorů: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada ^aff001; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada ^aff002; Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada ^aff003
Vyšlo v časopise: Role of α-Catenin and its mechanosensing properties in regulating Hippo/YAP-dependent tissue growth. PLoS Genet 15(11): e32767. doi:10.1371/journal.pgen.1008454
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1008454

Souhrn

α-catenin is a key protein of adherens junctions (AJs) with mechanosensory properties. It also acts as a tumor suppressor that limits tissue growth. Here we analyzed the function of Drosophila α-Catenin (α-Cat) in growth regulation of the wing epithelium. We found that different α-Cat levels led to a differential activation of Hippo/Yorkie or JNK signaling causing tissue overgrowth or degeneration, respectively. α-Cat can modulate Yorkie-dependent tissue growth through recruitment of Ajuba, a negative regulator of Hippo signaling to AJs but also through a mechanism independent of Ajuba recruitment to AJs. Both mechanosensory regions of α-Cat, the M region and the actin-binding domain (ABD), contribute to growth regulation. Whereas M is dispensable for α-Cat function in the wing, individual M domains (M1, M2, M3) have opposing effects on growth regulation. In particular, M1 limits Ajuba recruitment. Loss of M1 causes Ajuba hyper-recruitment to AJs, promoting tissue-tension independent overgrowth. Although M1 binds Vinculin, Vinculin it is not responsible for this effect. Moreover, disruption of mechanosensing of the α-Cat ABD affects tissue growth, with enhanced actin interactions stabilizing junctions and leading to tissue overgrowth. Together, our findings indicate that α-Cat acts through multiple mechanisms to control tissue growth, including regulation of AJ stability, mechanosensitive Ajuba recruitment, and dynamic direct F-actin interactions.

Klíčová slova:

Drosophila melanogaster – Hyperexpression techniques – Cell death – Epithelium – Lasers – Cytoskeleton – c-Jun N-terminal kinase signaling cascade

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