Human podocytes adhere to the KRGDS motif of the α3α4α5 collagen IV network

Podocyte adhesion to the glomerular basement membrane is required for proper function of the glomerular filtration barrier. However, the mechanism whereby podocytes adhere to collagen IV networks, a major component of the glomerular basement membrane, is poorly understood. The predominant collagen IV network is composed of triple helical protomers containing the alpha 3 alpha 4 alpha 5 chains. The protomers connect via the trimeric noncollagenous (NC1) domains to form hexamers at the interface. Because the NC1 domains of this network can potentially support integrin-dependent cell adhesion, it was determined whether individual NC1 monomers or alpha 3 alpha 4 alpha 5 hexamers support podocyte adhesion. It was found that, although human podocytes did not adhere to NC1 domains proper, they did adhere via integrin alpha v beta 3 to a KRGDS motif located adjacent to alpha 3NC1 domains. Because the KRGDS motif is a site of phosphorylation, its interactions with integrin alpha v beta 3 may play a critical role in cell signaling in physiologic and pathologic states.