Defective osteoblast function in ICAP-1-deficient mice.
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.
Bouvard
Daniel
D
Université Joseph Fourier, CNRS, UMR 5538, LEDAC, Institut Albert Bonniot, La Tronche Cedex, F-38706, France. daniel.bouvard@ujf-grenoble.fr
Aszodi
Attila
A
Kostka
Günter
G
Block
Marc R
MR
Albigès-Rizo
Corinne
C
Fässler
Reinhard
R
D000818:Animals; D001846:Bone Development; D002113:Calcification, Physiologic; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019465:Craniofacial Abnormalities / Q000235:genetics; D004392:Dwarfism / Q000235:genetics; D019012:Integrin beta1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
C512603:ICAP-1 protein, mouse; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D021122:Protein Subunits