Collagen XVI harbors an integrin α1β1 recognition site in its C-terminal domains

Collagen XVI is integrated tissue-dependently into distinct fibrillar aggregates, such as D-banded cartilage fibrils and fibrillin-1-containing microfibrils. In skin, the distribution of collagen XVI overlaps that of the collagen-binding integrins alpha 1 beta 1 and alpha 2 beta 1. Basal layer keratinocytes express integrin alpha 2 beta 1, whereas integrin alpha 1 beta 1 occurs in smooth muscle cells surrounding blood vessels, in hair follicles, and on adipocytes. Cells bearing the integrins alpha 1 beta 1 and alpha 2 beta 1 attach and spread on recombinant collagen XVI. Furthermore, collagen XVI induces the recruitment of these integrins into focal adhesion plaques, a principal step in integrin signaling. Of potential physiological relevance, these integrin-collagen XVI interactions may connect cells with specialized fibrils, thus contributing to the organization of fibrillar and cellular components within connective tissues. In cell-free binding assays, collagen XVI is more avidly bound by alpha 1 beta 1 integrin than by alpha 2 beta 1 integrin. Both integrins interact with collagen XVI via the A domain of their alpha subunits. A tryptic collagen XVI fragment comprising the collagenous domains 1 - 3 is recognized by alpha 1 beta 1 integrin. Electron microscopy of complexes of alpha 1 beta 1 integrin with this tryptic collagen XVI fragment or with full-length collagen XVI revealed a unique alpha 1 beta 1 integrin-binding site within collagen XVI located close to its C-terminal end.