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Basal spot junctions of Drosophila epithelial tissues respond to morphogenetic forces and regulate Hippo signaling
Developmental Cell ( IF 11.8 ) Pub Date : 2023-12-21 , DOI: 10.1016/j.devcel.2023.11.024
Benjamin Kroeger , Samuel A. Manning , Yoshana Fonseka , Viola Oorschot , Simon A. Crawford , Georg Ramm , Kieran F. Harvey

Organ size is controlled by numerous factors including mechanical forces, which are mediated in part by the Hippo pathway. In growing Drosophila epithelial tissues, cytoskeletal tension influences Hippo signaling by modulating the localization of key pathway proteins to different apical domains. Here, we discovered a Hippo signaling hub at basal spot junctions, which form at the basal-most point of the lateral membranes and resemble adherens junctions in protein composition. Basal spot junctions recruit the central kinase Warts via Ajuba and E-cadherin, which prevent Warts activation by segregating it from upstream Hippo pathway proteins. Basal spot junctions are prominent when tissues undergo morphogenesis and are highly sensitive to fluctuations in cytoskeletal tension. They are distinct from focal adhesions, but the latter profoundly influences basal spot junction abundance by modulating the basal-medial actomyosin network and tension experienced by spot junctions. Thus, basal spot junctions couple morphogenetic forces to Hippo pathway activity and organ growth.



中文翻译:

果蝇上皮组织的基底点连接响应形态发生力并调节 Hippo 信号传导

器官大小受多种因素控制,包括机械力,部分由 Hippo 通路介导。在生长的果蝇上皮组织中,细胞骨架张力通过调节关键通路蛋白在不同顶端区域的定位来影响 Hippo 信号传导。在这里,我们在基底点连接处发现了一个 Hippo 信号中枢,该连接点形成于侧膜的最基底点,在蛋白质组成方面类似于粘附连接。基底点连接通过 Ajuba 和 E-钙粘蛋白招募中央激酶 Warts,通过将其与上游 Hippo 通路蛋白分离来防止 Warts 激活。当组织经历形态发生时,基底点连接非常突出,并且对细胞骨架张力的波动高度敏感。它们与粘着斑不同,但后者通过调节基底-内侧肌动球蛋白网络和点连接所经历的张力来深刻影响基底点连接丰度。因此,基底点连接将形态发生力与 Hippo 通路活性和器官生长结合起来。

更新日期:2023-12-21
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