Tyrosine-Based Signals Regulate the Assembly of Daple⋅PARD3 Complex at Cell-Cell Junctions

• Published in: iScience Vol. 23; no. 2; p. 100859
• Main Authors: Ear, Jason, Saklecha, Anokhi, Rajapakse, Navin, Choi, Julie, Ghassemian, Majid, Kufareva, Irina, Ghosh, Pradipta
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.02.2020; Elsevier
• Subjects: Biological Sciences; Cell Biology; Functional Aspects of Cell Biology; Biological Sciences; Functional Aspects of Cell Biology; Cell Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.100859

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. We demonstrate that the protein 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. Furthermore, these processes may be mediated through interaction with the polarity regulator PARD3. This interaction, mediated by Daple's PDZ-binding motif (PBM) and the third PDZ domain of PARD3, is fine-tuned by tyrosine phosphorylation on Daple's PBM by receptor and non-receptor tyrosine kinases, such as Src. Hypophosphorylation strengthens the interaction, whereas hyperphosphorylation disrupts it, thereby revealing an unexpected role of Daple as a platform for signal integration and gradient sensing for tyrosine-based signals within the planar cell polarity pathway. [Display omitted] •Daple localizes to cell junction, regulates planar cell migration•Localization requires Daple's C-terminal PDZ-binding motif (PBM)•The PBM binds a PDZ module of the polarity determinant PARD3•The Daple⋅PARD3 interaction is regulated by tyrosine-based signals Biological Sciences; Cell Biology; Functional Aspects of Cell Biology