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The C terminus of talin links integrins to cell cycle progression

Pengbo Wang1, Christoph Ballestrem, Charles H Streuli

  • 1Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, England, UK.

The Journal of Cell Biology
|November 2, 2011
PubMed

Insights

Talin is crucial for cell adhesion signaling and proliferation. This study shows talin

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Integrins are key cell adhesion receptors sensing the extracellular matrix (ECM).
  • The precise mechanisms by which integrins initiate intracellular signaling remain incompletely understood.
  • Talin acts as a critical adapter protein at cell-matrix attachment sites, mediating outside-in signaling.

Purpose of the Study:

  • To investigate the role of talin in outside-in signaling initiated by integrins.
  • To elucidate how talin links integrin-mediated adhesion to intracellular events, including cell proliferation.

Main Methods:

  • Depletion of talin in mammary epithelial cells using lentiviral small hairpin ribonucleic acid (shRNA).
  • Assessment of cell adhesion, spreading, and actin cytoskeleton organization.
  • Analysis of the recruitment of focal adhesion proteins (vinculin, paxillin, FAK, ILK) to adhesion sites.
  • Functional assays to evaluate proliferation defects and cell cycle progression in talin-deficient cells.
  • Rescue experiments by reexpressing specific talin domains.

Main Results:

  • Talin-deficient cells maintained integrin-dependent adhesion and spreading with normal actin cytoskeleton.
  • Recruitment of key focal adhesion proteins including vinculin, paxillin, focal adhesion kinase (FAK), and integrin-linked kinase was abolished.
  • Talin deficiency led to significant proliferation defects and altered cell cycle progression.
  • Reexpression of the talin rod's C-terminal domain, but not the head domain, rescued FAK phosphorylation, suppressed p21 expression, and restored cell cycle progression.

Conclusions:

  • Talin is essential for recruiting and activating focal adhesion proteins necessary for cell proliferation.
  • The C-terminal region of the talin rod domain plays a critical role in linking integrin adhesions to cell cycle progression.
  • This study identifies a novel function for talin in connecting integrin-mediated cell-matrix interactions with cell cycle regulation.

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