Talin-dependent integrin activation is required for fibrin clot retraction by platelets.
Talin functions both as a regulator of integrin affinity and as an important mechanical link between integrins and the cytoskeleton. Using genetic deletion of talin, we show for the first time that the capacity of talin to activate integrins is required for fibrin clot retraction by platelets. To further dissect which talin functions are required for this process, we tested clot retraction in platelets expressing a talin1(L325R) mutant that binds to integrins, but exhibits impaired integrin activation ascribable to disruption of the interaction between talin and the membrane-proximal region (MPR) in the β-integrin cytoplasmic domain. Talin-deficient and talin1(L325R) platelets were defective in retracting fibrin clots. However, the defect in clot retraction in talin1(L325R) platelets, but not talin-deficient platelets, was rescued by extrinsically activating integrins with manganese, thereby proving that integrin activation is required and showing that talin1(L325R) can form functional links to the actin cytoskeleton.
Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Jacob R
JR
Haling
Susan J
SJ
Monkley
David R
DR
Critchley
Brian G
BG
Petrich
D000199:Actins / Q000378:metabolism; D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002846:Chromatography, Affinity; D003018:Clot Retraction / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D016608:Talin / Q000502:physiology*
D000199:Actins; D016023:Integrins; D016608:Talin; C496077:Tln1 protein, mouse; D005337:Fibrin