Talin distribution and phosphorylation in thrombin-activated platelets.
We have previously demonstrated that the subcellular distribution of the adhesion plaque protein, talin, changes dramatically in human platelets in response to platelet activation (Beckerle et al., J. Cell Biol. 109, 3333-3346, 1989). Talin is uniformly distributed throughout the cytoplasm of resting platelets. However, when platelets are stimulated to become activated and adhesive, a significant amount of the talin population rapidly redistributes to a peripheral, submembranous location. In the present study we have examined talin phosphorylation and proteolytic cleavage as possible mechanisms by which talin's subcellular distribution could be regulated in platelets. We have found that thrombin activation of platelets leads to a fourfold increase in talin phosphorylation. Proteolytic cleavage of talin, however, is not detected in washed platelets activated with thrombin for as long as 30 minutes. Because talin moves to a submembranous location upon platelet activation and has been shown to interact with integrins in vitro, we also investigated whether the major platelet integrin, GPIIb-IIIa, is required for talin redistribution. Using Glanzmann thrombasthenic platelets, which are deficient in GPIIb-IIIa, we found that talin redistribution occurs even in the absence of GPIIb-IIIa. Collectively, our studies suggest that neither proteolytic cleavage of talin nor interactions between talin and GPIIb-IIIa is required for the regulated redistribution of talin in thrombin-activated platelets. Phosphorylation of talin in response to thrombin activation may, however, be one mechanism utilized by platelets to regulate talin distribution and function in human platelets.
Bertagnolli
M E
ME
Department of Biology, University of Utah, Salt Lake City 84112.
Locke
S J
SJ
Hensler
M E
ME
Bray
P F
PF
Beckerle
M C
MC
D001692:Biological Transport; D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002451:Cell Compartmentation; D010450:Endopeptidases / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000502:physiology*; D016608:Talin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013915:Thrombasthenia / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D016023:Integrins; D016608:Talin; D010450:Endopeptidases; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium