Letter abstract
Nature Cell Biology 10, 314 - 321 (2008)
Published online: 10 February 2008 | doi:10.1038/ncb1693
Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2
Peng Ji1, Senthil Raja Jayapal1,2 & Harvey F. Lodish1
Mammalian erythroid cells undergo enucleation, an asymmetric cell division involving extrusion of a pycnotic nucleus enveloped by the plasma membrane1, 2, 3. The mechanisms that power and regulate the enucleation process have remained obscure. Here, we show that deregulation of Rac GTPase during a late stage of erythropoiesis completely blocks enucleation of cultured mouse fetal erythroblasts without affecting their proliferation or differentiation. Formation of the contractile actin ring (CAR) on the plasma membrane of enucleating erythroblasts was disrupted by inhibition of Rac GTPases. Furthermore, we demonstrate that mDia2, a downstream effector of Rho GTPases and a formin protein required for nucleation of unbranched actin filaments4, 5, 6, is also required for enucleation of mouse fetal erythroblasts. We show that Rac1 and Rac2 bind to mDia2 in a GTP-dependent manner and that downregulation of mDia2, but not mDia1, by small interfering RNA (siRNA) during the late stages of erythropoiesis blocked both CAR formation and erythroblast enucleation. Additionally, overexpression of a constitutively active mutant of mDia2 rescued the enucleation defects induced by the inhibition of Rac GTPases. These results reveal important roles for Rac GTPases and their effector mDia2 in enucleation of mammalian erythroblasts.
- Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Floor 6, Cambridge, MA 02142, USA.
- Current address: Stem Cell Group 4, Genome Institute of Singapore #08-01, Genome, 60 Biopolis Street, Singapore 138672.
Correspondence to: Harvey F. Lodish1 e-mail: lodish@wi.mit.edu
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