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Distinct localizations and roles of non-muscle myosin II during proplatelet formation and platelet release

I Badirou1, J Pan, S Souquere

  • 1Institut National de la Santé et de la Recherche Médicale, Villejuif, France; Université Paris-Sud, Le Kremlin-Bicêtre, France; Institut Gustave Roussy, Villejuif, France.

Journal of Thrombosis and Haemostasis : JTH
|March 5, 2015
PubMed
Abstract

Insights

Non-muscle myosin II-A (NMII-A) controls proplatelet (PPT) formation in megakaryocytes, unlike NMII-B. The N-terminal domain dictates NMII-A

Area of Science:

  • Hematology
  • Cell Biology
  • Molecular Biology

Background:

  • Megakaryocytes (MKs) extend proplatelets (PPTs) during maturation for platelet release.
  • Cytoskeletal rearrangements are crucial for PPT extension, organelle localization, and fragmentation.
  • Non-muscle myosin IIs (NMIIs), specifically NMII-A (MYH9), are implicated in PPT formation, while NMII-B (MYH10) is not found in mature MKs.

Purpose of the Study:

  • To investigate the in vivo roles of NMII-A and NMII-B in megakaryocyte PPT formation.
  • To elucidate the specific contributions of different NMII domains to platelet biogenesis.

Main Methods:

  • Utilized two transgenic mouse models.
  • Genetically replaced non-muscle myosin heavy chain (NMHC) II-A with NMHC II-B.
  • Created a chimeric NMHCII combining NMII-A head with NMII-B rod and tail domains.

Main Results:

  • Demonstrated that NMII-A's kinetic properties, influenced by its N-terminal domain, make it the preferred myosin for controlling PPT formation.
  • Showed that the carboxyl-terminal domain dictates NMII localization within the constriction region of PPTs.
  • Confirmed the carboxyl-terminal domain's responsibility for the specific role of NMII in platelet release.

Conclusions:

  • The N-terminal domain of NMII-A is critical for its function in PPT formation.
  • The carboxyl-terminal domain of NMII determines its localization and role in platelet release.
  • NMII-A is the key non-muscle myosin isoform regulating megakaryocyte proplatelet formation and platelet biogenesis.
Keywords:
Non-muscle myosin type IIANon-muscle myosin type IIBmegakaryocyteplateletstem cell

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