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

Karaköse E, Geiger T, Flynn K, Lorenz-Baath K, Zent R, Mann M, Fässler R
J Cell Sci. 2015 128 (5): 1023-33

PMID: 25609703 · PMCID: PMC4342583 · DOI:10.1242/jcs.162545

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.

© 2015. Published by The Company of Biologists Ltd.

MeSH Terms (13)

Adaptor Proteins, Signal Transducing Animals Cell Movement Cells, Cultured Cytoskeletal Proteins Focal Adhesions Integrins Keratinocytes LIM Domain Proteins Male Membrane Proteins Mice Mice, Transgenic

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