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Tyrosine‐based Signals Converge on Daple&[bull]PARD3 Complex to Fine‐tune Polarized Planar Cell Migration
Author(s) -
Ear Jason,
Saklecha Anokhi,
Rajapakse Navin,
Choi Julie,
Ghassemian Majid,
Kufareva Irina,
Ghosh Pradipta
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08628
Subject(s) - pdz domain , microbiology and biotechnology , cell polarity , cell growth , cell , pten , regulator , cell signaling , chemistry , hyperphosphorylation , signal transduction , biology , phosphorylation , pi3k/akt/mtor pathway , biochemistry , gene
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. This interaction, mediated by Daple’s PDZ‐binding motif (PBM) and the third PDZ domain of PARD3, is fine‐tuned by two tyrosine phosphoevents on Daple’s PBM that are triggered by a multitude of growth factors. 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. Support or Funding Information This paper was supported by NIH CA238042,CA100768 and CA160911 (to P.G). J.E was supported by an NCI/NIH‐funded Cancer Biology, Informatics & Omics (CBIO) Training Program (T32 CA067754) and a Postdoctoral Fellowship from the American Cancer Society (PF‐18‐101‐01‐CSM). I.K. was supported by NIH grants GM071872, AI118985, and GM117424.