The focal adhesion protein PINCH-1 associates with EPLIN at integrin adhesion sites

Esra Karaköse, Tamar Geiger, Kevin Flynn, Katrin Lorenz-Baath, Roy Zent, Matthias Mann, Reinhard Fässler

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

PINCH-1 is a LIM-only domain protein that forms a ternary complex with integrin-linked kinase (ILK and parvin (to form the IPP complex) downstream of integrins Here, we demonstrate that PINCH-1 (also known as Lims1) gene ablation in the epidermis of mice caused epidermal detachment from the basement membrane, epidermal hyperthickening and progressive hair loss. PINCH-1- deficient keratinocytes also displayed profound adhesion, spreading and migration defects in vitro that were substantially more severe than those of ILK-deficient keratinocytes indicating that PINCH-1 also exerts functions in an ILK-independent manner. By isolating the PINCH-1 interactome, the LIM-domain-containing and actin-binding protein epithelial protein lost in neoplasm (EPLIN, also known as LIMA1) was identified as a new PINCH-1-associated protein. EPLIN localized, in a PINCH-1-dependent manner, to integrin adhesion sites of keratinocytes in vivo and in vitro and its depletion severely attenuated keratinocyte spreading and migration on collagen and fibronectin without affecting PINCH-1 levels in focal adhesions. Given that the low PINCH-1 levels in ILK-deficient keratinocytes were sufficient to recruit EPLIN to integrin adhesions, our findings suggest that PINCH-1 regulates integrin-mediated adhesion of keratinocytes through the interactions with ILK as well as EPLIN.

Original languageEnglish
Pages (from-to)1023-1033
Number of pages11
JournalJournal of Cell Science
Volume128
Issue number5
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • EPLIN
  • Focal adhesion
  • Integrin
  • Keratinocyte
  • LIMA1
  • LIMS1
  • PINCH-1
  • Skin

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