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. PLSCR1 emergency granulopoiesis cell cycle mitosis nuclear trafficking Footnotes SEE CORRESPONDING EDITORIAL ON PAGE 215 ΔNLS-PLSCR1 mutation in the nuclear localization signal motif of phospholipid scramblase 1 ΔPal-PLSCR1 mutation at sites of palmitoylation of phospholipid scramblase 1 ANC absolute neutrophil count Band N. band neutrophils CMP common myeloid progenitors CTSG cathepsin G ER-Hoxb8 ER-binding domain-Hoxb8 fusion protein GMP granulocytic/monocytic-restricted progenitors GRI lymphocyte antigen 6 G/C LF lactoferrin Lin lineage-specific antigens Mac1 macrophage antigen 1 MEP megakaryocytic/erythroid-restricted progenitors MPO myeloperoxidase MSCV murine stem cell virus NLS nuclear localization signaling PLSCR1 phospholipid scramblase 1 PLSCR1–/– PLSCR1-knockout pMIG p-murine stem cell virus-IRES-GFP qPCR quantitative PCR Sca-1 lymphocyte antigen 6 A/E SCF stem cell factor Seg. N. segmented neutrophils SV similarity value YFP-ΔPal-PLSCR1 YFP and mutation at sites of palmitoylation of phospholipid scramblase 1 fusion construct YFP-PLSCR1 YFP and phospholipid scramblase 1 fusion construct Received January 5, 2011. Revision received February 17, 2011. Accepted February 26, 2011. © 2011 Society for Leukocyte Biology Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? Related articles Editorials : Hal E. Broxmeyer and Ivo P. Touw Editorial: Scrambling for a response to G-CSF J Leukoc Biol August 2011 90 : 215 - 216 ; doi: 10.1189/jlb.0311138 Discussion on the implications of new mechanistic data on G-CSF effects on neutrophil differentiation. Full Text Full Text (PDF) « Previous | Next Article » Table of Contents This Article Published online before print March 29, 2011 , doi: 10.1189/jlb.0111006 August 2011 Journal of Leukocyte Biology vol. 90 no. 2 221-233 » Abstract Full Text Full Text (PDF) All Versions of this Article: jlb.0111006v1 90/2/221 most recent Classifications Spotlight on Leading Edge Research Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Chen, C. Articles by Sims, P. J. Search for related content PubMed PubMed citation Articles by Chen, C. Articles by Sims, P. J. Related Content Related articles in this journal Load related web page information Sharing Email this article to a colleague Facebook Google+ LinkedIn Mendeley Reddit StumbleUpon Technorati Twitter What's this? 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