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

iScience (Feb 2020)

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

Journal volume & issue: Vol. 23, no. 2

Abstract

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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

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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