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First published online 12 May 2009
doi: 10.1242/jcs.044602

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Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation

Fabio Stanchi^1,2, Carsten Grashoff^2,*, Carine Flore Nguemeni Yonga^1,*, Dominique Grall¹, Reinhard Fässler² and Ellen Van Obberghen-Schilling^1,

¹ Institute of Developmental Biology and Cancer Research, University of Nice-Sophia Antiopolis, CNRS-UMR6543, Centre Antoine Lacassagne, 33 Avenue de Valombrose, 06189 Nice, France
² Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany

Author for correspondence (e-mail: vanobber{at}unice.fr)

Accepted 18 February 2009

Integrin-linked kinase (ILK) and cytoplasmic adaptors of the PINCH and parvin families form a ternary complex, termed IPP, that localizes to integrin adhesions. We show here that deletion of the genes encoding ILK or PINCH1 similarly blocks maturation of focal adhesions to tensin-rich and phosphotyrosine-poor fibrillar adhesions (FBs) by downregulating expression or recruitment of tensin and destabilizing 5β1-integrin–cytoskeleton linkages. As IPP components are interdependent for integrin targeting and protein stability, functional dissection of the complex was achieved by fusing ILK, PINCH, parvin or their individual motifs to the cytoplasmic tail of β3 integrin, normally excluded from FBs. Using this novel gain-of-function approach, we demonstrated that expression of the C-terminal kinase domain of ILK can restore tensin recruitment and prompt focal-adhesion maturation in IPP-null cells. Debilitating mutations in the paxillin- or ATP-binding sites of ILK, together with -parvin silencing, revealed a determinant role for ILK-parvin association, but not for direct paxillin binding, in this function. We propose a model in which the C-terminal domain of ILK promotes integrin sorting by reinforcing 5β1-integrin–actin linkage and controls force transmission by targeting tensin to maturing adhesions.

Key words: Integrins, Cell adhesions, Integrin linked kinase

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