Bouvard Daniel, Aszodi Attila, Kostka Günter, Block Marc R, Albigès-Rizo Corinne, Fässler Reinhard
Université Joseph Fourier, CNRS, UMR 5538, LEDAC, Institut Albert Bonniot, La Tronche Cedex, F-38706, France.
Development. 2007 Jul;134(14):2615-25. doi: 10.1242/dev.000877. Epub 2007 Jun 13.
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 beta1 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 beta1 integrin activation. Finally, we provide evidence that ICAP-1 promotes differentiation of osteoprogenitors by supporting their condensation through modulating the integrin high affinity state.
整合素受体家族通过募集辅助分子在细胞间和细胞与细胞外基质的相互作用中发挥重要作用。其中之一，整合素胞质结构域相关蛋白-1（ICAP-1；也称为ITGB1BP1），特异性地与β1整合素亚基的胞质结构域相互作用，并在体外负向调节其功能。为了研究ICAP-1在体内的作用，我们在小鼠中敲除了Icap-1基因。我们报道了ICAP-1在骨骼发育过程中对成骨细胞功能的意外作用。Icap-1基因缺失的小鼠成骨细胞增殖减少，骨矿化延迟，导致骨缝形成迟缓。体外研究表明，原代和永生化的Icap-1基因缺失的成骨细胞在细胞外基质底物上表现出增强的黏附和铺展，这可能是由于β1整合素激活增加所致。最后，我们提供证据表明，ICAP-1通过调节整合素的高亲和力状态来支持骨祖细胞的聚集，从而促进其分化。
