Mechanosensitive expression of lamellipodin promotes intracellular stiffness, cyclin expression and cell proliferation

Joseph A. Brazzo*, John C. Biber, Erik Nimmer, Yuna Heo, Linxuan Ying, Ruogang Zhao, Kwonmoo Lee, Matthias Krause, Yongho Bae

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Cell cycle control is a key aspect of numerous physiological and pathological processes. The contribution of biophysical cues, such as stiffness or elasticity of the underlying extracellular matrix (ECM), is critically important in regulating cell cycle progression and proliferation. Indeed, increased ECM stiffness causes aberrant cell cycle progression and proliferation. However, the molecular mechanisms that control these stiffness-mediated cellular responses remain unclear. Here, we address this gap and show good evidence that lamellipodin (symbol RAPH1), previously known as a critical regulator of cell migration, stimulates ECM stiffness-mediated cyclin expression and intracellular stiffening in mouse embryonic fibroblasts. We observed that increased ECM stiffness upregulates lamellipodin expression. This is mediated by an integrin-dependent FAK-Cas-Rac signaling module and supports stiffness-mediated lamellipodin induction. Mechanistically, we find that lamellipodin overexpression increased, and lamellipodin knockdown reduced, stiffness-induced cell cyclin expression and cell proliferation, and intracellular stiffness. Overall, these results suggest that lamellipodin levels may be critical for regulating cell proliferation.

Original languageEnglish
Article numberjcs257709
JournalJournal of Cell Science
Volume134
Issue number12
DOIs
Publication statusPublished - Jun 2021

Keywords

  • ECM stiffness
  • FAK
  • Lamellipodin
  • Mechanobiology
  • Proliferation
  • Rac

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