Exposure of plasminogen and a novel plasminogen receptor, Plg-RKT, on activated human and murine platelets

Claire S. Whyte, Gael B. Morrow, Nagyung Baik, Nuala A. Booth, Mohammed M. Jalal, Robert Parmer, Lindsey Miles, Nicola J Mutch* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Plasminogen activation rates are enhanced by cell surface binding. We have previously demonstrated that exogenous plasminogen binds to phosphatidylserine-exposing and spread platelets. Platelets contain plasminogen in their α-granules but secretion of plasminogen from platelets
has not been studied. Recently, a novel transmembrane lysine-dependent plasminogen receptor, Plg-RKT , has been described on macrophages. Here, we analyzed the pool of plasminogen in platelets and examined whether platelets express Plg-RKT. Plasminogen content of the supernatant of resting and collagen/thrombin-stimulated platelets was similar. Pre-treatment with the lysine analogue, εACA, significantly increased platelet-derived plasminogen (0.33 nmol/10 8 plts vs. 0.08 nmol/10 8 plts) in the stimulated supernatant, indicating a lysine-dependent mechanism of membrane retention. Lysine-dependent, platelet-derived plasminogen retention on thrombin and convulxin activated human platelets was confirmed by flow cytometry. Platelets initiated fibrinolytic activity in fluorescently labelled plasminogen-deficient clots and in turbidimetric clot lysis assays. A 17 kDa band, consistent with Plg-RKT, was detected in the platelet membrane fraction by Western blotting. Confocal microscopy of stimulated platelets revealed Plg-RKT co-localized with platelet-derived plasminogen on the activated platelet membrane.
Plasminogen exposure was significantly attenuated in thrombin and convulxin stimulated platelets from Plg-RKT -/- mice compared to wild type (WT) littermates. Membrane exposure of Plg-RKT was not dependent on plasminogen, as similar levels of the receptor were detected in plasminogen -/- platelets. These data highlight Plg-RKT as a novel plasminogen receptor in human and murine platelets. We show for the first time that platelet-derived plasminogen is retained on the activated platelet membrane and drives local fibrinolysis, by enhancing cell-surface mediated plasminogen activation.
Original languageEnglish
Pages (from-to)248–257
Number of pages26
Issue number2
Early online date25 Aug 2020
Publication statusPublished - 14 Jan 2021

Bibliographical note

The authors thank the Microscopy and Histology Core Facility and the Iain Fraser Cytometry at the University of Aberdeen for excellent advice and use of facilities. We thank Dr.Victoria Ploplis, University of Notre Dame for kindly providing mice deficient in plasminogen. This study was supported by grants from the British Heart Foundation PG/15/82/31721 (C.S.W & N.J.M), British Society for Haematology, Thrombosis UK, British Society of Haemostasis & Thrombosis Joint PhD Studentship (G.B.M, C.S.W, N.J.M), University of Tabuk PhD Studentship (M.M.J & N.J.M), NIH HL-081046 (to L.A.M.), and HL149511 (to R.J.P. and
L.A.M.) and by Merit Review Award I01BX003933 from the U.S. Department of Veterans Affairs (to R.J.P.).


  • plasminogen
  • Plg-RKT
  • platelets
  • fibrinolysis


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