Distinct but critical roles for integrin alphaIIbbeta3 in platelet lamellipodia formation on fibrinogen, collagen-related peptide and thrombin.
Integrins are the major receptor type known to facilitate cell adhesion and lamellipodia formation on extracellular matrix proteins. However, collagen-related peptide and thrombin have recently been shown to mediate platelet lamellipodia formation when presented as immobilized surfaces. The aims of this study were to establish if there exists a role for the platelet integrin alpha(IIb)beta(3) in this response; and if so, whether signalling from the integrin is required for lamellipodia formation on these surfaces. Real-time analysis was used to compare platelet morphological changes on surfaces of fibrinogen, collagen-related peptide or thrombin in the presence of various pharmacological inhibitors and platelets from 'knockout' mice. We demonstrate that collagen-related peptide and thrombin stimulate distinct patterns of platelet lamellipodia formation and elevation of intracellular Ca(2+) to that induced by the integrin alpha(IIb)beta(3) ligand, fibrinogen. Nevertheless, lamellipodia formation on collagen-related peptide and thrombin is dependent upon engagement of alpha(IIb)beta(3), consistent with release of alpha(IIb)beta(3) ligand(s) from platelet granules. However, the requirement for signalling by the integrin on fibrinogen can be bypassed by the addition of thrombin to the solution. These observations reveal a critical role for alpha(IIb)beta(3) in forming lamellipodia on collagen-related peptide and thrombin which is dependent on its ability to function as an adhesive receptor but not necessarily on its ability to signal. These results suggest that integrins may play an important role in lamellipodia formation triggered by nonintegrin ligands in platelets and possibly in other cell types.
Thornber
Kelly
K
Department of Biochemistry, University of Oxford, UK.
McCarty
Owen J T
OJ
Watson
Steve P
SP
Pears
Catherine J
CJ
D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D005340:Fibrinogen / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000097:blood; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051966:Phospholipase C gamma / Q000235:genetics / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011554:Pseudopodia / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology*
D002352:Carrier Proteins; D038982:Integrin alpha2beta1; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C435908:collagen-related peptide; D005340:Fibrinogen; D051966:Phospholipase C gamma; D013917:Thrombin; D002118:Calcium