Fibronectin isoforms in megakaryocytes

P K Schick1, C M Wojensk, V Bennett

  • 1Cardeza Foundation for Hematologic Research and the Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5099, USA.

Insights

Megakaryocytes (MKs) synthesize fibronectin EIIIB, a form crucial for cell maturation. This fibronectin variant is found on MK surfaces after thrombin stimulation, suggesting a role in MK migration and maturation.

Area of Science:

  • Cell Biology
  • Hematology
  • Biochemistry

Background:

  • Fibronectin (FN) and its alternatively spliced variant, FN EIIIB, are important in cell development and migration.
  • Megakaryocytes (MKs) are the cells responsible for platelet production.
  • FN EIIIB is typically found in embryonic and developing cells, with limited presence in adult tissues.

Purpose of the Study:

  • To investigate the synthesis and localization of fibronectin (FN) and FN EIIIB in megakaryocytes (MKs).
  • To determine the effect of thrombin on FN and FN EIIIB secretion and localization in MKs.
  • To explore the potential role of cell-surface bound FN EIIIB in MK function.

Main Methods:

  • Immunohistochemistry and confocal microscopy were used to analyze FN and FN EIIIB expression in MKs.
  • Bone marrow cells were treated with thrombin to observe changes in fibronectin localization.
  • Analysis focused on differentiating between secreted and cell-surface bound fibronectin.

Main Results:

  • Megakaryocytes (MKs) synthesize both general fibronectin (FN) and the alternatively spliced FN EIIIB.
  • Unlike general FN, thrombin stimulation does not cause the secretion of FN EIIIB into the medium.
  • Both general FN and FN EIIIB accumulate on the MK surface after thrombin treatment, indicating cell-surface binding rather than release into the extracellular space.

Conclusions:

  • Megakaryocytes (MKs) and platelets are among the few adult cell types that synthesize and contain fibronectin EIIIB.
  • Thrombin induces the cell-surface binding of FN EIIIB on MKs, suggesting it is released to bind the cell surface.
  • The presence and localization of FN EIIIB on the MK surface may play a specific role in megakaryocyte migration and maturation processes.

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