Tyrosine-Based Signals Regulate the Assembly of Daple⋅PARD3 Complex at Cell-Cell Junctions
Jason Ear,
Anokhi Saklecha,
Navin Rajapakse,
Julie Choi,
Majid Ghassemian,
Irina Kufareva,
Pradipta Ghosh
Affiliations
Jason Ear
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA; Corresponding author
Anokhi Saklecha
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA
Navin Rajapakse
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA
Julie Choi
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA
Majid Ghassemian
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
Irina Kufareva
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA
Pradipta Ghosh
Department of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA; Department of Medicine, University of California San Diego, 9500 Gilman Drive (MC 0651), George E. Palade Bldg, Rm 331-333, La Jolla, CA 92093, USA; Rebecca and John Moore Comprehensive Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; Veterans Affairs Medical Center, La Jolla, CA, USA; Corresponding author
Summary: 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. : Biological Sciences; Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Functional Aspects of Cell Biology
