Human podocytes adhere to the KRGDS motif of the alpha3alpha4alpha5 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 alpha3alpha4alpha5 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 alpha3alpha4alpha5 hexamers support podocyte adhesion. It was found that, although human podocytes did not adhere to NC1 domains proper, they did adhere via integrin alphavbeta3 to a KRGDS motif located adjacent to alpha3NC1 domains. Because the KRGDS motif is a site of phosphorylation, its interactions with integrin alphavbeta3 may play a critical role in cell signaling in physiologic and pathologic states.
Borza
Corina M
CM
Vanderbilt Medical Center, Nashville, TN 37232, USA.
Borza
Dorin-Bogdan
DB
Pedchenko
Vadim
V
Saleem
Moin A
MA
Mathieson
Peter W
PW
Sado
Yoshikazu
Y
Hudson
Heather M
HM
Pozzi
Ambra
A
Saus
Juan
J
Abrahamson
Dale R
DR
Zent
Roy
R
Hudson
Billy G
BG
D020816:Amino Acid Motifs; D000818:Animals; D002448:Cell Adhesion; D024141:Collagen Type IV; D006801:Humans; D050199:Podocytes / Q000502:physiology*
D024141:Collagen Type IV