Mammalian erythroblast enucleation requires PI3K-dependent cell polarization

Junxia Wang, Tzutzuy Ramirez, Peng Ji, Senthil Raja Jayapal, Harvey F. Lodish, Maki Murata-Hori*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Enucleation, the final step in terminal differentiation of mammalian red blood cells, is an essential process in which the nucleus surrounded by the plasma membrane is budded off from the erythroblast to form a reticulocyte. Most molecular events in enucleation remain unclear. Here we show that enucleation requires establishment of cell polarization that is regulated by the microtubule-dependent local activation of phosphoinositide 3-kinase (PI3K). When the nucleus becomes displaced to one side of the cell, actin becomes restricted to the other side, where dynamic cytoplasmic contractions generate pressure that pushes the viscoelastic nucleus through a narrow constriction in the cell surface, forming a bud. The PI3K products PtdIns(3,4)P2 and PtdIns(3,4,5)P3 are highly localized at the cytoplasmic side of the plasma membrane. PI3K inhibition caused impaired cell polarization, leading to a severe delay in enucleation. Depolymerization of microtubules reduced PI3K activity, resulting in impaired cell polarization and enucleation. We propose that enucleation is regulated by microtubules and PI3K signaling in a manner mechanistically similar to directed cell locomotion.

Original languageEnglish (US)
Pages (from-to)340-349
Number of pages10
JournalJournal of cell science
Issue number2
StatePublished - Jan 15 2012


  • Cell polarization
  • Erythroblast enucleation
  • Microtubules
  • PI3-kinase

ASJC Scopus subject areas

  • Cell Biology


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