Integrin alpha 11 beta 1 is a receptor for collagen XIII

Abstract

Collagen XIII is a conserved transmembrane collagen mainly expressed in mesenchymal tissues. Previously, we have shown that collagen XIII modulates tissue development and homeostasis. Integrins are a family of receptors that mediate signals from the environment into the cells and vice versa. Integrin alpha 11 beta 1 is a collagen receptor known to recognize the GFOGER (O=hydroxyproline) sequence in collagens. Interestingly, collagen XIII and integrin alpha 11 beta 1 both have a role in the regulation of bone homeostasis. To study whether alpha 11 beta 1 is a receptor for collagen XIII, we utilized C2C12 cells transfected to express alpha 11 beta 1 as their only collagen receptor. The interaction between collagen XIII and integrin alpha 11 beta 1 was also confirmed by surface plasmon resonance and pull-down assays. We discovered that integrin alpha 11 beta 1 mediates cell adhesion to two collagenous motifs, namely GPKGER and GF(S)QGEK, that were shown to act as the recognition sites for the integrin alpha 11-I domain. Furthermore, we studied the in vivo significance of the alpha 11 beta 1-collagen XIII interaction by crossbreeding alpha 11 null mice (Itga11(-/-)) with mice overexpressing Col13a1 (Col13a1(oe)). When we evaluated the bone morphology by microcomputed tomography, Col13a1(oe) mice had a drastic bone overgrowth followed by severe osteoporosis, whereas the double mutant mouse line showed a much milder bone phenotype. To conclude, our data identifies integrin alpha 11 beta 1 as a new collagen XIII receptor and demonstrates that this ligand-receptor pair has a role in the maintenance of bone homeostasis.