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Updated: Feb 6, 2026

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
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In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

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Mechano-Dependent Phosphorylation of the PDZ-Binding Motif of CD97/ADGRE5 Modulates Cellular Detachment

Doris Hilbig1, Doreen Sittig1, Franz Hoffmann1

  • 1Department of Surgery, Research Laboratories, Leipzig University, Leipzig, Germany.

Cell Reports
|August 23, 2018
PubMed

Insights

Mechanical forces phosphorylate CD97/ADGRE5 at its PDZ-binding motif, disrupting cell adhesion. This CD97 motif is crucial for cellular mechanical responses and cytoskeleton linkage.

Area of Science:

  • Cell Biology
  • Biophysics

Background:

  • Cells dynamically respond to mechanical forces through complex signaling networks.
  • The cell adhesion molecule CD97/ADGRE5 plays a role in cellular processes, but its mechanical regulation is not fully understood.

Purpose of the Study:

  • To investigate the role of CD97/ADGRE5 phosphorylation in cellular responses to mechanical stress.
  • To elucidate the mechanism by which CD97/ADGRE5 mediates cellular mechanotransduction.

Main Methods:

  • Utilized biochemical assays to analyze CD97/ADGRE5 phosphorylation and its interaction with DLG1.
  • Employed shear stress experiments on cells expressing wild-type and mutant CD97/ADGRE5.
  • Investigated CD97/ADGRE5 localization and cellular morphology under mechanical load.

Main Results:

  • Mechanical forces induce rapid phosphorylation of CD97/ADGRE5 at its C-terminal PDZ-binding motif (PBM).
  • Phosphorylation disrupts CD97/ADGRE5 binding to the DLG1 scaffold protein, leading to altered cell adhesion and membrane dynamics.
  • Cells lacking the PBM exhibit increased deformability and faster loss of cell contacts under shear stress, indicating the PBM's critical role in mechanotransduction.
  • CD97/ADGRE5 is linked to the cytoskeleton in an F-actin-dependent manner.

Conclusions:

  • CD97/ADGRE5 phosphorylation at the PBM is a key event in cellular mechanotransduction.
  • The PBM of CD97/ADGRE5 is essential for regulating cell stiffness, cell-cell adhesion, and cytoskeletal organization under mechanical stress.
  • CD97/ADGRE5 modulates cellular mechanoresponse through signaling alterations mediated by its PBM.
Keywords:
CD97PDZ-binding motifadherens junctiondetachmentmechanotransductionshear stress

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