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First published online 13 June 2007
doi: 10.1242/dev.000877
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1 Université Joseph Fourier, CNRS, UMR 5538, LEDAC, Institut Albert
Bonniot, La Tronche Cedex, F-38706, France.
2 INSERM, U823, Equipe DySAD, Institut Albert Bonniot, F-38042, France.
3 Max Planck Institut für Biochemie, Department of Molecular Medicine, Am
Klopferspitz 18a, 82152 Martinsried, Germany.
* Author for correspondence (e-mail: daniel.bouvard{at}ujf-grenoble.fr)
Accepted 4 May 2007
The integrin receptor family plays important roles in cell-to-cell and cell-to-extracellular matrix interactions through the recruitment of accessory molecules. One of them, the integrin cytoplasmic domain-associated protein-1 (ICAP-1; also known as ITGB1BP1), specifically interacts with the cytoplasmic domain of the ß1 integrin subunit and negatively regulates its function in vitro. To address the role of ICAP-1 in vivo, we ablated the Icap-1 gene in mice. We report an unexpected role of ICAP-1 in osteoblast function during bone development. Icap-1-deficient mice suffer from reduced osteoblast proliferation and delayed bone mineralization, resulting in the retarded formation of bone sutures. In vitro studies reveal that primary and immortalized Icap-1-null osteoblasts display enhanced adhesion and spreading on extracellular matrix substrates, probably owing to an increase in ß1 integrin activation. Finally, we provide evidence that ICAP-1 promotes differentiation of osteoprogenitors by supporting their condensation through modulating the integrin high affinity state.
Key words: ICAP-1 (ITGB1BP1), Integrin, Cell differentiation, Cell adhesion, Osteoblast, Mouse
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