Osteoblast mineralization requires β1 integrin/ICAP-1-dependent fibronectin deposition
The morphogenetic and differentiation events required for bone formation are orchestrated by diffusible and insoluble factors that are localized within the extracellular matrix. In mice, the deletion of ICAP-1, a modulator of β1 integrin activation, leads to severe defects in osteoblast proliferatio...
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Main Authors: | , , , , , , , |
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Format: | Article (Journal) |
Language: | English |
Published: |
2011
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In: |
The journal of cell biology
Year: 2011, Volume: 194, Issue: 2, Pages: 307-322 |
ISSN: | 1540-8140 |
DOI: | 10.1083/jcb.201007108 |
Online Access: | lizenzpflichtig![]() |
Author Notes: | Molly Brunner, Angélique Millon-Frémillon, Genevieve Chevalier, Inaam A. Nakchbandi, Deane Mosher, Marc R. Block, Corinne Albigès-Rizo and Daniel Bouvard |
Summary: | The morphogenetic and differentiation events required for bone formation are orchestrated by diffusible and insoluble factors that are localized within the extracellular matrix. In mice, the deletion of ICAP-1, a modulator of β1 integrin activation, leads to severe defects in osteoblast proliferation, differentiation, and mineralization and to a delay in bone formation. Deposition of fibronectin and maturation of fibrillar adhesions, adhesive structures that accompany fibronectin deposition, are impaired upon ICAP-1 loss, as are type I collagen deposition and mineralization. Expression of β1 integrin with a mutated binding site for ICAP-1 recapitulates the ICAP-1-null phenotype. Follow-up experiments demonstrated that ICAP-1 negatively regulates kindlin-2 recruitment onto the β1 integrin cytoplasmic domain, whereas an excess of kindlin-2 binding has a deleterious effect on fibrillar adhesion formation. These results suggest that ICAP-1 works in concert with kindlin-2 to control the dynamics of β1 integrin-containing fibrillar adhesions and, thereby, regulates fibronectin deposition and osteoblast mineralization. |
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Item Description: | Gesehen am 28.06.2021 |
Physical Description: | Online Resource |
ISSN: | 1540-8140 |
DOI: | 10.1083/jcb.201007108 |