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

doi:10.1016/j.isci.2020.100859

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

iScience. 2020 Feb 21;23(2):100859. doi: 10.1016/j.isci.2020.100859. Epub 2020 Jan 22.

Authors

Jason Ear¹, Anokhi Saklecha², Navin Rajapakse², Julie Choi², Majid Ghassemian³, Irina Kufareva⁴, Pradipta Ghosh⁵

Affiliations

¹ 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. Electronic address: jaear@ucsd.edu.
² 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.
³ Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
⁴ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
⁵ 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. Electronic address: prghosh@ucsd.edu.

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. 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.

Keywords: Biological Sciences; Cell Biology; Functional Aspects of Cell Biology.

Abstract

Grants and funding