The force-sensitive protein Ajuba regulates cell adhesion during epithelial morphogenesis

Abstract

The reorganization of cells in response to mechanical forces converts simple epithelial sheets into complex tissues of various shapes and dimensions. Epithelial integrity is maintained throughout tissue remodeling, but the mechanisms that regulate dynamic changes in cell adhesion under tension are not well understood. In , planar polarized actomyosin forces direct spatially organized cell rearrangements that elongate the body axis. We show that the LIM-domain protein Ajuba is recruited to adherens junctions in a tension-dependent fashion during axis elongation. Ajuba localizes to sites of myosin accumulation at adherens junctions within seconds, and the force-sensitive localization of Ajuba requires its N-terminal domain and two of its three LIM domains. We demonstrate that Ajuba stabilizes adherens junctions in regions of high tension during axis elongation, and that Ajuba activity is required to maintain cell adhesion during cell rearrangement and epithelial closure. These results demonstrate that Ajuba plays an essential role in regulating cell adhesion in response to mechanical forces generated by epithelial morphogenesis.

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

“…One possibility is that mechanical force distributed over fewer α-Cat molecules enhances the mechanosensory response of individual α-Cat molecules in a non-linear manner resulting in higher Jub recruitment. Evidence for such a mechanism was recently reported for the recruitment of Vinc to AJs in the Drosophila germband [Kale et al, 2018], and may be similar for Jub recruitment to AJ in that tissue [Razzell et al, 2018]. Fourth, removing the entire M region results in an α-Cat protein that can support normal wing development, implying that M region mechanosensing is not an essential aspect of regulating tissue growth.…”

“…The tension generated by cytoskeletal forces recruits Jub to AJs [Razzell et al 2018., Rauskolb et al, 2014 and modulates cell proliferation in the wing disc [Eder et al, 2016]. That some α-Cat mutant isoforms induce increased tension is a possible explanation for the excessive recruitment of Jub.…”

Multicellular Rosettes Drive Fluid-solid Transition in Epithelial Tissues

“…Under periodic boundary conditions, the network will always obey Euler's characteristic formula V − E þ F ¼ 0, where V and E are the number of vertices and edges, respectively. The density of higher-order vertices is captured by the average vertex coordination number, given by extended periods of time [43,44,58,59]. We also perform an alternative set of simulations in which T1 and T2 (cell apoptosis) transitions are allowed as shown in Fig.…”

The Drosophila Afadin and ZO-1 homologs Canoe and Polychaetoid act in parallel to maintain epithelial integrity when challenged by adherens junction remodeling

“…A different speculative possibility is that Afadin and ZO-1 proteins form part of a single large and multivalent protein complex, but recruit into this complex different, nonredundant partners, making loss of both more deleterious than loss of either one alone. Future work, including super-resolution imaging of Pyd and Cno, and identification and functional analysis of different binding partners may help resolve these mechanistic questions, and also help define what other proteins act in parallel or together with them-one intriguing candidate is the mechanosensitive junctional protein Jub/Ajuba (Razzell et al, 2018;Rauskolb et al, 2019) Defining interacting partners and parallel mechanisms for maintaining epithelial integrity is an important future direction.…”