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Scientific article
Open access
English

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

Published inJournal of Cell Science, vol. 132, no. 8, jcs224493
Publication date2019
Abstract

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.

Keywords
  • Adhesion
  • FRAP
  • Fibrillar adhesions
  • Fibronectin
  • Focal adhesions
  • Integrins
  • Isoform
  • Muscle
  • Paxillin
  • Splicing
  • Talin1
  • Talin2
Funding
  • Swiss National Science Foundation - 31003A 146283
  • Swiss National Science Foundation - 31003A 166384
Citation (ISO format)
SOTO RIBEIRO, Martinho et al. β1D integrin splice variant stabilizes integrin dynamics and reduces integrin signaling by limiting paxillin recruitment. In: Journal of Cell Science, 2019, vol. 132, n° 8, p. jcs224493. doi: 10.1242/jcs.224493
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Article (Published version)
Identifiers
ISSN of the journal0021-9533
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Technical informations

Creation12/02/2019 9:49:00 AM
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