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

• DOI: 10.1016/j.celrep.2018.07.071
• Publication Date: 2018-08-24T18:15:53Z
• Authors: Doris Hilbig; Doreen Sittig; Franz Hoffmann; Sven Rothemund; Enrico Warmt; Marianne Quaas; Julia Stürmer; Liane Seiler; Ines Liebscher; Ngoc Anh Hoang; Josef A. Käs; Lawrence Banks; Gabriela Aust
• Keywords: PDZ domain

Cells respond to mechanical stimuli with altered signaling networks. Here, we show that forces rapidly induce phosphorylation of CD97/ADGRE5 (pCD97) at its intracellular C-terminal PDZ-binding motif (PBM). Biochemically, this disrupts CD97 binding PDZ domains the scaffold protein DLG1. In shear-stressed cells, pCD97 appears not only in junctions, retracting fibers, and attachment area but also lost membrane patches, demonstrating (intra)cellular detachment PBM. This is critical for CD97-dependent mechanoresponse. expressing without PBM are more deformable, under shear stress, these cells lose cell contacts faster changes actin cytoskeleton when compared full-length CD97. Our data indicate linkage cytoskeleton. Consistently, knockout phenocopies PBM, membranous organized an F-actin-dependent manner. summary, shapes cellular mechanoresponse through modulation via