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Role of Gukholder in adhesion in the Drosophila wing disc Ho, Rosalie

Abstract

Cell adhesion plays an important role in maintaining tissue homeostasis and morphogenesis. In Drosophila, adhesion between neighbouring cells is mediated by adhesion junctions (AJ) and septate junctions (SJ) whereas the focal adhesion complex (FAC) adheres cells to the extracellular matrix. At the convergence of three neighbouring cells, a specialized junction is formed—the tricellular junction (TCJ). Both SJs and TCJs contribute to the formation of permeability barriers. Discs large (Dlg) and Scribble (Scrib) are scaffolding proteins responsible for recruiting the TCJ proteins Gliotactin and Anakonda. However, the mechanism that recruits Dlg and Scrib to the TCJ is not known. In the neuromuscular junction, Gukholder (Gukh) binds to the guanylate kinase (GUK) domain in Dlg, via the Dlg-binding domain, to facilitate the recruitment of Scrib. Thus, Gukh may mediate the recruitment of Dlg and Scrib to the TCJ. We found that within the wing imaginal disc epithelia Gukh is expressed at multiple locations including the SJ and TCJ, basolateral to the TCJ, and adjacent to the FAC on the basal side of the epithelium. We found that the knockdown of Gukh triggers severe cellular phenotypes including JNK-mediated apoptosis, cell migration, and cell delamination. However, Gukh is not necessary for the formation of the TCJ, SJ, or the FAC as RNAi-mediate knockdown of Gukh did not affect these junctional domains. Rather, TCJ proteins recruit Gukh to the TCJ, and β-integrin recruits Gukh to the basal domain. The exception was the lateral or intermediate zone where Gukh not only associated with the FAC but where loss of Gukh disrupted the recruitment of the FAC proteins as did overexpression of the Gukh C-terminal domain. This suggests a model where Gukh mediates the localization of focal adhesion-like structures in the lateral domain. Overall, we propose that Gukh is recruited to the TCJ and basal focal adhesion complex by two independent processes, and functions to mediate adhesion in the lateral domain.

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