title: Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition.
abstract: 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.
authors.affiliation: Equipe 1 Dynamique des Systèmes d'Adhérence et Différenciation Cellulaire, Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, Cedex 09, France.
authors.forename: Molly
authors.initials: M
authors.lastname: Brunner
authors.forename: Angélique
authors.initials: A
authors.lastname: Millon-Frémillon
authors.forename: Genevieve
authors.initials: G
authors.lastname: Chevalier
authors.forename: Inaam A
authors.initials: IA
authors.lastname: Nakchbandi
authors.forename: Deane
authors.initials: D
authors.lastname: Mosher
authors.forename: Marc R
authors.initials: MR
authors.lastname: Block
authors.forename: Corinne
authors.initials: C
authors.lastname: Albigès-Rizo
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouvard
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D003598:Cytoskeletal Proteins; D005353:Fibronectins; C512603:ICAP-1 protein, mouse; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C527802:kindlin-2 protein, mouse