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bioRxiv · 10.1101/717041

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.
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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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Ear, J., Saklecha, A., Ghassemian, M., Kufareva, I., Ghosh, P.. 2019-07-27. Tyrosine-based Signals Converge on Daple*PARD3 Complex to Fine-tune Polarized Planar Cell Migration. https://doi.org/10.1101/717041

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