title: Nuclear phospholipid scramblase 1 prolongs the mitotic expansion of granulocyte precursors during G-CSF-induced granulopoiesis.
abstract: PLSCR1-/- mice exhibit normal, steady-state hematologic parameters but impaired emergency granulopoiesis upon in vivo administration of G-CSF. The mechanism by which PLSCR1 contributes to G-CSF-induced neutrophil production is largely unknown. We now report that the expansion of bone marrow myelocytes upon in vivo G-CSF treatment is reduced in PLSCR1-/- mice relative to WT. Using SCF-ER-Hoxb8-immortalized myeloid progenitors to examine the progression of G-CSF-driven granulocytic differentiation in vitro, we found that PLSCR1 prolongs the period of mitotic expansion of proliferative granulocyte precursors, thereby giving rise to increased neutrophil production from their progenitors. This effect of PLSCR1 is blocked by a ΔNLS-PLSCR1, which prevents its nuclear import. By contrast, mutation that prevents the membrane association of PLSCR1 has minimal impact on the role of PLSCR1 in G-CSF-induced granulopoiesis. These data imply that the capacity of PLSCR1 to augment G-CSF-dependent production of mature neutrophils from myeloid progenitors is unrelated to its reported activities at the endofacial surface of the plasma membrane but does require entry of the protein into the nucleus, suggesting that this response is mediated through the observed effects of PLSCR1 on gene transcription.
authors: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: Chun-Wei
authors: CW
authors: Chen
authors: Mark
authors: M
authors: Sowden
authors: Qian
authors: Q
authors: Zhao
authors: Therese
authors: T
authors: Wiedmer
authors: Peter J
authors: PJ
authors: Sims
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D049109:Cell Proliferation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology*; D019891:Leukopoiesis / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D023461:Myeloid Progenitor Cells / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D049294:Phospholipid Transfer Proteins / Q000172:deficiency / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D049294:Phospholipid Transfer Proteins; C493426:Plscr1 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor