β1D integrin splice variant stabilizes integrin dynamics and reduces integrin signaling by limiting paxillin recruitment

Article Article scientifique Article β1D integrin splice variant stabilizes integrin dynamics and reduces integrin signaling by limiting paxillin recruitment eng 2019 author Soto Ribeiro Martinho 586241 author Kastberger Birgit 744149 author Bachmann Michaël 910175 author Azizi Latifeh author Fouad Kenza 862108 author Jacquier-Schupbach Marie Claude 118964 author Boettiger David 695343 author Bouvard Daniel author Bastmeyer Martin author Hytönen Vesa P author Wehrle-Haller Bernhard 0000-0002-1159-1147 116298 jcs224493 10.1242/jcs.224493 30890648 0021-9533 https://jcs.biologists.org/content/132/8/jcs224493.long Heterodimeric integrin receptors control cell adhesion, migration and extracellular matrix assembly. While the α integrin subunit determines extracellular ligand specificity, the β integrin chain binds to an acidic residue of the ligand, and cytoplasmic adapter protein families such as talins, kindlins and paxillin, to form mechanosensing cell matrix adhesions. Alternative splicing of the β1 integrin cytoplasmic tail creates ubiquitously expressed β1A, and the heart and skeletal muscle-specific β1D form. To study the physiological difference between these forms, we developed fluorescent β1 integrins and analyzed their dynamics, localization, and cytoplasmic adapter recruitment and effects on cell proliferation. On fibronectin, GFP-tagged β1A integrin showed dynamic exchange in peripheral focal adhesions, and long, central fibrillar adhesions. In contrast, GFP-β1D integrins exchanged slowly, forming immobile and short central adhesions. While adhesion recruitment of GFP-β1A integrin was sensitive to C-terminal tail mutagenesis, GFP-β1D integrin was recruited independently of the distal NPXY motif. In addition, a P786A mutation in the proximal, talin-binding NPXY783 motif switched β1D to a highly dynamic integrin. In contrast, the inverse A786P mutation in β1A integrin interfered with paxillin recruitment and proliferation. Thus, differential β1 integrin splicing controls integrin-dependent adhesion signaling, to adapt to the specific physiological needs of differentiated muscle cells. Adhesion FRAP Fibrillar adhesions Fibronectin Focal adhesions Integrins Isoform Muscle Paxillin Splicing Talin1 Talin2 Dewey 612 Swiss National Science Foundation 31003A 146283 CH Swiss National Science Foundation 31003A 166384 CH 134 Département de physiologie cellulaire et métabolisme 21C false 379 Migration cellulaire 645 Journal of Cell Science 132 8 5870277d-1943-4e0a-aaa5-15fbcf7c5d9c Article (Published version) Public Soto-Ribeiro_jcs224493-2019.pdf 6524192 application/pdf OA OTHER Restricted 2020-06-02 openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

Title	Published in	Year	Views	Downloads

Metabolic Modulation of The β1 Integrin Acetylation Modulates Fibroblasts Adhesions, Growth and Fibronectin Assembly		2020	554	1
β1D integrin splice variant stabilizes integrin dynamics and reduces integrin signaling by limiting paxillin recruitment	Journal of Cell Science	2019	717	246

Archive ouverte UNIGE

Fouad, Kenza