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bioRxiv · 10.1101/2022.05.18.492492

Rap1 uses Canoe-dependent and Canoe-independent mechanisms to regulate apical contractility and allow embryonic morphogenesis without tissue disruption

Perez-Vale, K. Z.·Yow, K. D.·Greene, M.·Gurley, N. J.·Peifer, M.
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Abstract

Embryonic morphogenesis is powered by dramatic changes in cell shape and arrangement, driven by the cytoskeleton and its connections to adherens junctions. This requires robust linkage, allowing morphogenesis without disrupting tissue integrity. The small GTPase Rap1 is a key regulator of cell adhesion, controlling both cadherin-mediated and integrin-mediated processes. We have defined multiple roles in morphogenesis for one Rap1 effector, Canoe/Afadin, which ensures robust junction-cytoskeletal linkage. We now ask what mechanisms regulate Canoe and other junction-cytoskeletal linkers during Drosophila morphogenesis, defining roles for Rap1 and one of its guanine nucleotide exchange factor (GEF) regulators, Dizzy. Rap1 uses Canoe as one effector, regulating junctional planar polarity. However, Rap1 has additional roles in junctional protein localization and balanced apical constriction--in its absence, Bazooka/Par3 localization is fragmented, and cells next to mitotic cells apically constrict and invaginate, disrupting epidermal integrity. In contrast, the GEF Dizzy has phenotypes similar to but slightly less severe than Canoe loss, suggesting this GEF regulates Rap1 action via Canoe. Taken together, these data reveal that Rap1 is a crucial regulator of morphogenesis, likely acting in parallel via Canoe and other effectors, and that different Rap1 GEFs regulate distinct functions of Rap1.

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Perez-Vale, K. Z., Yow, K. D., Greene, M., Gurley, N. J., Peifer, M.. 2022-05-18. Rap1 uses Canoe-dependent and Canoe-independent mechanisms to regulate apical contractility and allow embryonic morphogenesis without tissue disruption. https://doi.org/10.1101/2022.05.18.492492

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