Tyrosine-based Signals Converge on Daple*PARD3 Complex to Fine-tune Polarized Planar Cell Migration
Ear, J.; Saklecha, A.; Ghassemian, M.; Kufareva, I.; Ghosh, P.
Show abstract
Polarized distribution of organelles and molecules inside a cell is vital for a range of cellular processes and its loss is frequently encountered in disease. Polarization during planar cell migration is a special condition in which cellular orientation is triggered by cell-cell contact. Here, we demonstrate that the multi-modular signaling scaffold Daple (CCDC88C) is a component of cell junctions in epithelial cells which serves like a cellular compass for establishing and maintaining contact-triggered planar polarity via its interaction with the polarity regulator PARD3, which has been implicated in both apical-basal and planar polarity. This interaction, mediated by Daples PDZ-binding motif (PBM) and the third PDZ domain of PARD3, is fine-tuned by two tyrosine phosphoevents on Daples PBM that are known to be triggered by a multitude of receptor and non-receptor tyrosine kinases, such as Src. Hypophosphorylation strengthens the interaction, whereas hyperphosphorylation disrupts it. These findings reveal an unexpected role of Daple within the planar cell polarity pathway as a platform for signal integration and gradient sensing for tyrosine-based signals.
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