Article

A specific alpha5beta1-integrin conformation promotes directional integrin translocation and fibronectin matrix formation.

Craniofacial Developmental Biology and Regeneration Branch, NIDCR, NIH, Bethesda, MA 20892, USA.
Journal of Cell Science (impact factor: 6.11). 02/2005; 118(Pt 2):291-300. DOI:10.1242/jcs.01623
Source: PubMed

ABSTRACT Integrin adhesion receptors are structurally dynamic proteins that adopt a number of functionally relevant conformations. We have produced a conformation-dependent anti-alpha5 monoclonal antibody (SNAKA51) that converts alpha5beta1 integrin into a ligand-competent form and promotes fibronectin binding. In adherent fibroblasts, SNAKA51 preferentially bound to integrins in fibrillar adhesions. Clustering of integrins expressing this activation epitope induced directional translocation of alpha5beta1, mimicking fibrillar adhesion formation. Priming of alpha5beta1 integrin by SNAKA51 increased the accumulation of detergent-resistant fibronectin in the extracellular matrix, thus identifying an integrin conformation that promotes matrix assembly. The SNAKA51 epitope was mapped to the calf-1/calf-2 domains. We propose that the action of the antibody causes the legs of the integrin to change conformation and thereby primes the integrin to bind ligand. These findings identify SNAKA51 as the first anti-integrin antibody to selectively recognize a subset of adhesion contacts, and they identify an integrin conformation associated with integrin translocation and fibronectin matrix formation.

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Keywords

adherent fibroblasts
 
adhesion contacts
 
alpha5beta1 integrin
 
antibody causes
 
bind ligand
 
calf-1/calf-2 domains
 
change conformation
 
conformation-dependent anti-alpha5 monoclonal antibody
 
converts alpha5beta1 integrin
 
extracellular matrix
 
fibrillar adhesions
 
fibronectin matrix formation
 
first anti-integrin antibody
 
functionally relevant conformations
 
Integrin adhesion receptors
 
integrin conformation
 
ligand-competent form
 
mimicking fibrillar adhesion formation
 
promotes matrix assembly
 
SNAKA51 epitope