title: The focal adhesion protein PINCH-1 associates with EPLIN at integrin adhesion sites.
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.
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Esra
authors.initials: E
authors.lastname: Karaköse
authors.affiliation: Department of Proteomics and Signal Transductions, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Tamar
authors.initials: T
authors.lastname: Geiger
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Flynn
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Lorenz-Baath
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt Medical Center, Nashville, TN, 37232, USA Department of Medicine, Nashville Veterans Affairs Medical Center, Nashville, TN, 37232, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
authors.affiliation: Department of Proteomics and Signal Transductions, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany faessler@biochem.mpg.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C485741:D15Ertd366e protein, mouse; D016023:Integrins; D060588:LIM Domain Proteins; C490232:Lims1 protein, mouse; D008565:Membrane Proteins
keywords: EPLIN; Focal adhesion; Integrin; Keratinocyte; LIMA1; LIMS1; PINCH-1; Skin