{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:10:31Z","timestamp":1775855431780,"version":"3.50.1"},"reference-count":39,"publisher":"The Company of Biologists","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,15]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1242\/jcs.088286","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T01:46:44Z","timestamp":1329184004000},"page":"340-349","source":"Crossref","is-referenced-by-count":50,"title":["Mammalian erythroblast enucleation requires PI3K-dependent cell polarization"],"prefix":"10.1242","volume":"125","author":[{"given":"Junxia","family":"Wang","sequence":"first","affiliation":[{"name":"Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzutzuy","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Ji","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biological Research, Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Floor 6, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senthil Raja","family":"Jayapal","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biological Research, Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Floor 6, Cambridge, MA 02142, USA"},{"name":"Stem Cell Group 4, Genome Institute of Singapore, #08-01, Genome, 60 Biopolis Street, Singapore 138672"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey F.","family":"Lodish","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biological Research, Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Floor 6, Cambridge, MA 02142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Murata-Hori","sequence":"additional","affiliation":[{"name":"Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, 117604, Singapore"},{"name":"Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042522252504500_R1","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nrm2453","article-title":"Blebs lead the way: how to migrate without lamellipodia","volume":"9","author":"Charras","year":"2008","journal-title":"Nat. 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