Collagen-platelet interactions: recognition and signalling.
The collagen-platelet interaction is central to haemostasis and may be a critical determinant of arterial thrombosis, where subendothelium is exposed after rupture of atherosclerotic plaque. Recent research has capitalized on the cloning of an important signalling receptor for collagen, glycoprotein VI, which is expressed only on platelets, and on the use of collagen-mimetic peptides as specific tools for both glycoprotein VI and integrin alpha 2 beta 1. We have identified sequences, GPO and GFOGER (where O denotes hydroxyproline), within collagen that are recognized by the collagen receptors glycoprotein VI and integrin alpha 2 beta 1 respectively, allowing their signalling properties and specific functional roles to be examined. Triple-helical peptides containing these sequences were used to show the signalling potential of integrin alpha 2 beta 1, and to confirm its important contribution to platelet adhesion. Glycoprotein VI appears to operate functionally on the platelet surface as a dimer, which recognizes GPO motifs that are separated by four triplets of collagen sequence. These advances will allow the relationship between the structure of collagen and its haemostatic activity to be established.
Farndale
Richard W
RW
Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, U.K. rwf10@cam.ac.uk
Siljander
Pia R
PR
Onley
David J
DJ
Sundaresan
Pavithra
P
Knight
C Graham
CG
Barnes
Michael J
MJ
D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D015398:Signal Transduction
D003094:Collagen