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Dynamins 2 and 3 control the migration of human megakaryocytes by regulating CXCR4 surface expression and ITGB1

Praveen K Suraneni1, Seth J Corey2,3,4,5, Michael J Hession2

  • 1Department of Medicine and.

Blood Advances
|December 13, 2018
PubMed

Insights

Dynamins (DNMs) regulate megakaryocyte (MK) migration by controlling endocytosis and receptor trafficking. Inhibiting DNMs impairs MK movement toward vascular niches, impacting proplatelet formation.

Area of Science:

  • Hematopoiesis
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Megakaryocyte (MK) migration from bone marrow to circulation is crucial for platelet production.
  • The precise molecular mechanisms governing MK directional migration remain largely unknown.

Purpose of the Study:

  • To investigate the role of dynamins (DNMs) in regulating megakaryocyte (MK) migration.
  • To elucidate how DNM activity influences cytoskeletal dynamics, receptor trafficking, and cell movement.

Main Methods:

  • Utilized dynasore (DNSR) inhibitor and short hairpin RNA (shRNA) to target DNM2 and DNM3 in human MK cell lines and primary MKs.
  • Assessed actin polymerization, RhoA activity, CXCR4 surface expression, and β1 integrin (ITGB1) activity.
  • Examined Rab11 localization to evaluate endosomal recycling pathways.

Main Results:

  • DNM inhibition impaired directional MK migration and reduced actin polymerization and RhoA activity.
  • DNM inhibition increased CXCR4 surface expression due to reduced endocytosis.
  • DNM inhibition diminished ITGB1 activity and disrupted Rab11-marked recycling endosome trafficking.

Conclusions:

  • Dynamin GTPase activity is critical for MK migration by regulating endocytosis and receptor trafficking.
  • DNMs control membrane-cytoskeleton rearrangements downstream of CXCR4 and integrins, guiding MKs toward vascular niches.

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