The Asymmetric Cell Division Regulators Par3, Scribble and Pins/Gpsm2 Are Not Essential for Erythroid Development or Enucleation

Wölwer, Christina B.; Gödde, Nathan; Pase, Luke; Elsum, Imogen; Lim, Krystle Y.B.; Sacirbegovic, Faruk; Walkley, Carl R.; Ellis, Sarah; Ohno, Shigeo; Matsuzaki, Fumio; Russell, Sarah M.; Humbert, Patrick O.

doi:10.1371/journal.pone.0170295

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…Conditional knockout suggests that Scribble plays a similar role in hematopoietic stem cell maintenance (Mohr et al, 2018). In contrast, it does not play a similar role in the erythrocyte lineage (Wölwer et al, 2017). One challenge for future work is to define proteins with which Scribble works in asymmetric division-the only identified partner in this process is GUKh (Albertson and Doe, 2003).…”

Section: Polarizing Mitosis: Roles For Scribble In Asymmetric Cell Divisionmentioning

confidence: 99%

Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation

Bonello

Peifer

2018

Journal of Cell Biology

114

110

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Key events ranging from cell polarity to proliferation regulation to neuronal signaling rely on the assembly of multiprotein adhesion or signaling complexes at particular subcellular sites. Multidomain scaffolding proteins nucleate assembly and direct localization of these complexes, and the protein Scribble and its relatives in the LAP protein family provide a paradigm for this. Scribble was originally identified because of its role in apical–basal polarity and epithelial integrity in Drosophila melanogaster. It is now clear that Scribble acts to assemble and position diverse multiprotein complexes in processes ranging from planar polarity to adhesion to oriented cell division to synaptogenesis. Here, we explore what we have learned about the mechanisms of action of Scribble in the context of its multiple known interacting partners and discuss how this knowledge opens new questions about the full range of Scribble protein partners and their structural and signaling roles.

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Section: Polarizing Mitosis: Roles For Scribble In Asymmetric Cell Divisionmentioning

confidence: 99%

Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation

Bonello

Peifer

2018

Journal of Cell Biology

114

110

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“…Erythroblast enucleation and asymmetric cell division were also compared. Asymmetric cell division regulators were not required for erythroblast enucleation 10 . In addition, histone deacetylases, proteasomal regulators, mitogen-activated protein kinases, and cyclin-dependent kinases were identified as molecules involved in erythroblast enucleation using a novel chemical screening approach 11 .…”

Section: Introductionmentioning

confidence: 95%

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

Ubukawa

Goto

Asanuma

et al. 2020

Sci Rep

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The molecular mechanisms involved in the terminal differentiation of erythroblasts have been elucidated by comparing enucleation and cell division. Although various similarities and differences between erythroblast enucleation and cytokinesis have been reported, the mechanisms that control enucleation remain unclear. We previously reported that dynein and microtubule-organizing centers mediated the polarization of nuclei in human erythroblasts. Moreover, the accumulation of F-actin was noted during the enucleation of erythroblasts. Therefore, during enucleation, upstream effectors in the signal transduction pathway regulating dynein or actin, such as cell division control protein 42 homolog (Cdc42), may be crucial. We herein investigated the effects of the Cdc42 inhibitor, CASIN, on cytokinesis and enucleation in colony-forming units-erythroid (CFU-Es) and mature erythroblasts (day 10). CASIN blocked the proliferation of CFU-Es and their enucleation in a dose-dependent manner. Dynein adopted an island-like distribution in the cytoplasm of non-treated CFU-Es, but was concentrated near the nucleus as a dot and co-localized with γ-tubulin in CASIN-treated cells. CASIN blocked the accumulation of F-actin in CFU-Es and day 10 cells. These results demonstrated that Cdc42 plays an important role in cytokinesis, nuclear polarization and nuclear extrusion through a relationship with dynein and actin filament organization during the terminal differentiation of erythroblasts.

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“…Enucleation can be viewed as a form of asymmetric cell division. However, analysis of mice lacking wellcharacterized regulators of neuroblast asymmetric cell division led to the conclusion that neither Par3, Scribble nor Pins/Gpsm2 play roles in erythroid enucleation (Wölwer et al 2017).…”

Section: Eccentricity Of the Condensed Nucleusmentioning

confidence: 99%

Cellular dynamics of mammalian red blood cell production in the erythroblastic island niche

2019

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Red blood cells, or erythrocytes, make up approximately a quarter of all cells in the human body with over 2 billion new erythrocytes made each day in a healthy adult human. This massive cellular production system is coupled with a set of cell biological processes unique to mammals, in particular, the elimination of all organelles, and the expulsion and destruction of the condensed erythroid nucleus. Erythrocytes from birds, reptiles, amphibians and fish possess nuclei, mitochondria and other organelles: erythrocytes from mammals lack all of these intracellular components. This review will focus on the dynamic changes that take place in developing erythroid cells that are interacting with specialized macrophages in multicellular clusters termed erythroblastic islands. Proerythroblasts enter the erythroblastic niche as large cells with active nuclei, mitochondria producing heme and energy, and attach to the central macrophage via a range of adhesion molecules. Proerythroblasts then mature into erythroblasts and, following enucleation, in reticulocytes. When reticulocytes exit the erythroblastic island, they are smaller cells, without nuclei and with few mitochondria, possess some polyribosomes and have a profoundly different surface molecule phenotype. Here, we will review, step-by-step, the biophysical mechanisms that regulate the remarkable process of erythropoiesis with a particular focus on the events taking place in the erythroblastic island niche. This is presented from the biological perspective to offer insight into the elements of red blood cell development in the erythroblastic island niche which could be further explored with biophysical modelling systems.

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The Asymmetric Cell Division Regulators Par3, Scribble and Pins/Gpsm2 Are Not Essential for Erythroid Development or Enucleation

Cited by 4 publications

References 33 publications

Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation

Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation

Cdc42 regulates cell polarization and contractile actomyosin rings during terminal differentiation of human erythroblasts

Cellular dynamics of mammalian red blood cell production in the erythroblastic island niche

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