scholarly journals Mutation of the nuclear pore complex component, aladin1, disrupts asymmetric cell division in Zea mays (maize)

2021 ◽  
Author(s):  
Norman B Best ◽  
Charles Addo-Quaye ◽  
Bong-Suk Kim ◽  
Clifford F Weil ◽  
, Burkhard Schulz ◽  
...  
Keyword(s):  
Cell Division ◽  
Nuclear Pore Complex ◽  
Asymmetric Cell Division ◽  
Genetic Diseases ◽  
Nuclear Pore ◽  
Rna Seq ◽  
Transcript Accumulation ◽  
Shoot Architecture ◽  
Asymmetric Divisions ◽  
Mother Cells

Abstract The nuclear pore complex (NPC) regulates the movement of macromolecules between the nucleus and cytoplasm. Dysfunction of many components of the NPC results in human genetic diseases, including triple A syndrome (AAAS) as a result of mutations in ALADIN. Here we report a nonsense mutation in the maize ortholog, aladin1 (ali1-1), at the orthologous amino acid residue of an AAAS allele from humans, alters plant stature, tassel architecture, and asymmetric divisions of subsidiary mother cells (SMCs). Crosses with the stronger nonsense allele ali1-2 identified complex allele interactions for plant height and aberrant SMC division. RNA-seq analysis of the ali1-1 mutant identified compensatory transcript accumulation for other NPC components as well as gene expression consequences consistent with conservation of ALADIN1 functions between humans and maize. These findings demonstrate that ALADIN1 is necessary for normal plant development, shoot architecture, and asymmetric cell division in maize.

scholarly journals Mutation of the nuclear pore complex component, aladin1, disrupts asymmetric cell division in Zea mays (maize)

2020 ◽  
Author(s):  
Norman B. Best ◽  
Charles Addo-Quaye ◽  
Bong-Suk Kim ◽  
Clifford F. Weil ◽  
Burkhard Schulz ◽  
...  
Keyword(s):  
Cell Division ◽  
Nuclear Pore Complex ◽  
Asymmetric Cell Division ◽  
Genetic Diseases ◽  
Nuclear Pore ◽  
Rna Seq ◽  
Transcript Accumulation ◽  
Shoot Architecture ◽  
Asymmetric Divisions ◽  
Mother Cells

AbstractThe nuclear pore complex (NPC) regulates the movement of macromolecules between the nucleus and cytoplasm. Dysfunction of many components of the NPC results in human genetic diseases, including triple A syndrome (AAAS) as a result of mutations in ALADIN. Here we report a nonsense mutation in the maize ortholog, aladin1 (ali1-1), at the orthologous amino acid residue of an AAAS allele from humans, alters plant stature, tassel architecture, and asymmetric divisions of subsidiary mother cells (SMCs). Crosses with the stronger nonsense allele ali1-2 identified complex allele interactions for plant height and aberrant SMC division. RNA-seq analysis of the ali1-1 mutant identified compensatory transcript accumulation for other NPC components as well as gene expression consequences consistent with conservation of ALADIN1 functions between humans and maize. These findings demonstrate that ALADIN1 is necessary for normal plant development, shoot architecture, and asymmetric cell division in maize.

scholarly journals Roles of Actin in the Morphogenesis of the Early Caenorhabditis elegans Embryo

2020 ◽  
Vol 21 (10) ◽  
pp. 3652
Author(s):  
Dureen Samandar Eweis ◽  
Julie Plastino
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Asymmetric Cell Division ◽  
Cell Types ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Asymmetric Cell Divisions ◽  
C Elegans ◽  
Asymmetric Divisions ◽  
Different Cell Types

The cell shape changes that ensure asymmetric cell divisions are crucial for correct development, as asymmetric divisions allow for the formation of different cell types and therefore different tissues. The first division of the Caenorhabditis elegans embryo has emerged as a powerful model for understanding asymmetric cell division. The dynamics of microtubules, polarity proteins, and the actin cytoskeleton are all key for this process. In this review, we highlight studies from the last five years revealing new insights about the role of actin dynamics in the first asymmetric cell division of the early C. elegans embryo. Recent results concerning the roles of actin and actin binding proteins in symmetry breaking, cortical flows, cortical integrity, and cleavage furrow formation are described.

scholarly journals The Snail protein family regulates neuroblast expression of inscuteable and string, genes involved in asymmetry and cell division in Drosophila

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4757-4767 ◽  
Author(s):  
Shovon I. Ashraf ◽  
Y. Tony Ip
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Division ◽  
System Development ◽  
Nervous System Development ◽  
Central Nervous System Development ◽  
Asymmetric Divisions ◽  
Snail Family ◽  
Snail Protein ◽  
Mother Cells

Delaminated neuroblasts in Drosophila function as stem cells during embryonic central nervous system development. They go through repeated asymmetric divisions to generate multiple ganglion mother cells, which divide only once more to produce postmitotic neurons. Snail, a zinc-finger transcriptional repressor, is a pan-neural protein, based on its extensive expression in neuroblasts. Previous results have demonstrated that Snail and related proteins, Worniu and Escargot, have redundant and essential functions in the nervous system. We show that the Snail family of proteins control central nervous system development by regulating genes involved in asymmetry and cell division of neuroblasts. In mutant embryos that have the three genes deleted, the expression of inscuteable is significantly lowered, while the expression of other genes that participate in asymmetric division, including miranda, staufen and prospero, appears normal. The deletion mutants also have much reduced expression of string, suggesting that a key component that drives neuroblast cell division is abnormal. Consistent with the gene expression defects, the mutant embryos lose the asymmetric localization of prospero RNA in neuroblasts and lose the staining of Prospero protein that is normally present in ganglion mother cells. Simultaneous expression of inscuteable and string in the snail family deletion mutant efficiently restores Prospero expression in ganglion mother cells, demonstrating that the two genes are key targets of Snail in neuroblasts. Mutation of the dCtBP co-repressor interaction motifs in the Snail protein leads to reduction of the Snail function in central nervous system. These results suggest that the Snail family of proteins control both asymmetry and cell division of neuroblasts by activating, probably indirectly, the expression of inscuteable and string.

Asymmetric cell division of thoracic neuroblast 6–4 to bifurcate glial and neuronal lineage in Drosophila

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1967-1974 ◽  
Author(s):  
Y. Akiyama-Oda ◽  
T. Hosoya ◽  
Y. Hotta
Keyword(s):  
Cell Division ◽  
Glial Cells ◽  
Daughter Cell ◽  
Asymmetric Cell Division ◽  
Cell Types ◽  
Cell Number ◽  
Protein Activity ◽  
Neuronal Lineage ◽  
Glial Fate ◽  
Mother Cells

In the development of the Drosophila central nervous system, some of the neuroblasts designated as neuroglioblasts generate both glia and neurons. Little is known about how neuroglioblasts produce these different cell types. NB6-4 in the thoracic segment (NB6-4T) is a neuroglioblast, although the corresponding cell in the abdominal segment (NB6-4A) produces only glia. Here, we describe the cell divisions in the NB6-4T lineage, following changes in cell number and cell arrangement. We also examined successive changes in the expression of glial cells missing (gcm) mRNA and protein, activity of which is known to direct glial fate from the neuronal default state. The first cell division of NB6-4T occurred in the medial-lateral orientation, and was found to bifurcate the glial and neuronal lineage. After division, the medial daughter cell expressed GCM protein to produce three glial cells, while the lateral daughter cell with no GCM expression produced ganglion mother cells, secondary precursors of neurons. Although gcm mRNA was present evenly in the cytoplasm of NB6-4T before the first cell division, it became detected asymmetrically in the cell during mitosis and eventually only in the medial daughter cell. In contrast, NB6-4A showed a symmetrical distribution of gcm mRNA and GCM protein through division. Our observations suggest that mechanisms regulating gcm mRNA expression and its translation play an important role in glial and neuronal lineage bifurcation that results from asymmetric cell division.

scholarly journals Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals “aging factors” and mechanism of lifespan asymmetry

2015 ◽  
Vol 112 (38) ◽  
pp. 11977-11982 ◽  
Author(s):  
Jing Yang ◽  
Mark A. McCormick ◽  
Jiashun Zheng ◽  
Zhengwei Xie ◽  
Mitsuhiro Tsuchiya ◽  
...  
Keyword(s):  
Cell Division ◽  
Asymmetric Cell Division ◽  
Asymmetric Distribution ◽  
Systematic Analysis ◽  
Daughter Cells ◽  
Yeast Proteome ◽  
Mother And Daughter ◽  
Asymmetric Partitioning ◽  
Mother Cells ◽  
Aging Factors

Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials (“aging factors”) through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter-enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms.

The Eukaryotic Translation Initiation Factor 4E (eIF4E) Has Oncogenic Functions and May Represent a New Therapeutic Target In Diffuse Large B Cell Lymphoma (DLBCL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3785-3785 ◽  
Author(s):  
Biljana Culjkovic ◽  
Tharu Fernando ◽  
ShaoNing Yang ◽  
Ari M. Melnick ◽  
Katherine LB Borden ◽  
...  
Keyword(s):  
Cell Lines ◽  
Nuclear Pore Complex ◽  
Nuclear Export ◽  
Therapeutic Approach ◽  
B Cell Lymphoma ◽  
Nuclear Pore ◽  
Molecular Heterogeneity ◽  
Rna Seq ◽  
Protein Levels ◽  
Target Transcript

Abstract DLBCL features marked molecular heterogeneity. Gene overexpression due to genetic lesions or by other mechanisms activates powerful oncogenic pathways such as MYC, BCL6, BCL2 and MCL1; that are usually expressed concomitantly. Regardless the underlying mechanism, genes must first be transcribed into mRNA and then translated into proteins in the cytosol to exert their oncogenic functions. While most transcripts representing bulk mRNA are exported to the cytosol using the TAP/NXF1 complex, a specific subset of transcripts that contain a conserved sequence (4E-SE) are exported using the eIF4E/LRPPRC/XPO1 complex. EIF4E is frequently elevated in many malignances and exhibit oncogenic potential that arises from its critical roles in the nuclear export and cytosolic translation of oncogenic transcripts. EIF4E competitive inhibitors, such as ribavirin (RIB), as well as XPO1 inhibitors such as KPT-330, abrogate its pro-survival function by decreasing export and translation of target mRNAs. We hypothesized that eIF4E could have a role in the expression of oncogenic transcripts and proteins in DLBCL patients. In this case, eIF4E nuclear pore complex inhibitors would constitute a new therapeutic approach for this disease. We first analyzed the expression of eIF4E in DLBCLs by gene expression (RNA-seq and qPCR) and immunohistochemistry (IHC). Compared to centroblasts, primary DLBCL (n=69) and cell lines (n=25) showed significant overexpression of eIF4E (p<0.0001 and p=0.04, respectively). IHC analysis of eIF4E in 75 DLBCL indicates that 72% of cases overexpressed eIF4E in either the nucleus, cytosol or both. BCL6, the most frequently involved oncogene in DLBCL, contains a 4E-SE sequence in its transcript making it a potential eIF4E target. To determine whether in fact BCL6 was an eIF4E target, we analyzed BCL6 transcript cytosolic/nuclear ratio (C/N) in DLBCL cells engineered to overexpress or knockdown eIF4E. eIF4E overexpression and knocking-down caused 80% increase and 40% decrease in BCL6 C/N respectively, and this was accompanied by coincident BCL6 protein changes. To further characterize the nuclear eIF4E contribution to BCL6 expression we infected DLBCL cells with control vector (GFP), eIEF4EWT (overexpression), eIF4EW73A (mutant with no translation activity) and eIF4ES53A (mutant with no export activity). Only eIEF4EWT and eIF4EW73Awere able to increase and maintain BCL6 mRNA and protein levels, suggesting that BCL6 is, at least, an export target of eIF4E. To more directly test this, we performed eIF4E-immunoprecipitation followed by RNA-seq or qPCR (for validation) in DoHH2 and SUDHL6 cells. We found that BCL6, together with other 150 transcripts including the oncogenes MYC, MCL1, BCL2, BCLXL and OCD1, was significantly and differentially bound to eIF4E (vs. IgG control) in both cell lines. Additional functional experiments validated these oncogenes transcripts as eIF4E targets in DLBCL cells. In DLBCLs with cytosolic eIF4E overexpression, BCL6 and other oncogenes with complex 5’UTRs, such as MYC, BCL2 and MCL1, could be also behave as preferential translational targets. In order to test this, we isolated nine polysomal fractions from SUDHL6 cells treated with RIB 30 μM or vehicle for up to 96 h. We found that RIB treatment significantly decreased BCL6, MYC, BCL2 and MCL1 transcripts in polysomes. Non-complex transcripts such as actin were unaffected. This translated in decreased protein levels of BCL6, MYC, BCL2 and MCL1 in treated cells. Our data therefore suggested that BCL6 is a new eIF4E target transcript and RIB decreases BCL6 transcript and subsequently protein levels by inhibiting both mRNA nuclear export and preferential translation. To assess whether this could be capitalized therapeutically, we exposed a panel of 10 DLBCL cell lines for 48 h to eIF4E nuclear pore complex inhibitors RIB and KPT-330. We found that RIB and KPT-330 have potent anti-lymphoma activity in these cells. We then tested this concept in vivo in established OCI-Ly1 xenografts that were randomized into 2 groups of 7 mice each and treated with vehicle or RIB 80 mg/kg/day. After 10 days of treatment, RIB significantly decreased tumor proliferation (p=0.025) without inducing toxicity. In sum, this study showed that BCL6 is a new eIF4E target transcript and that eIF4E nuclear pore complex inhibitors could represent a new therapeutic approach for DLBCL pts, especially for those with expression of multiple oncogenes. Disclosures: No relevant conflicts of interest to declare.

scholarly journals C. elegans Runx/CBFβ suppresses POP-1(TCF) to convert asymmetric to proliferative division of stem cell-like seam cells

2019 ◽  
Author(s):  
Suzanne E. M. van der Horst ◽  
Janine Cravo ◽  
Alison Woollard ◽  
Juliane Teapal ◽  
Sander van den Heuvel
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Time Lapse ◽  
Cell Number ◽  
Self Renewal ◽  
C Elegans ◽  
Cell Divisions ◽  
Seam Cell ◽  
Asymmetric Divisions

ABSTRACTA correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight in the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by non-canonical Wnt/β-catenin asymmetry signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy, we show that symmetric cell divisions maintain the asymmetric localization of Wnt/β-catenin pathway components. Observations based on lineage-specific knockout and GFP-tagging of endogenous pop-1 support the model that POP-1TCF induces differentiation at a high nuclear level, while low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator rnt-1Runx and cofactor bro-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, opposition between the C. elegans Runx/CBFβ and TCF stem-cell regulators controls the switch between asymmetric and symmetric seam cell division.

The Formation, Structure, Distribution and Frequency of Nuclear Pores

1971 ◽  
Vol 29 ◽  
pp. 518-519
Author(s):  
G. G. Maul
Keyword(s):  
Nuclear Pore Complex ◽  
Nuclear Membrane ◽  
Dynamic Structure ◽  
Nuclear Pore ◽  
Nuclear Pores ◽  
Filter Function ◽  
Etching Technique ◽  
Selective Filter ◽  
Membranous Part

The chromatin of eukaryotic cells is separated from the cytoplasm by a double membrane. One obvious structural specialization of the nuclear membrane is the presence of pores which have been implicated to facilitate the selective nucleocytoplasmic exchange of a variety of large molecules. Thus, the function of nuclear pores has mainly been regarded to be a passive one. Non-membranous diaphragms, radiating fibers, central rings, and other pore-associated structures were thought to play a role in the selective filter function of the nuclear pore complex. Evidence will be presented that suggests that the nuclear pore is a dynamic structure which is non-randomly distributed and can be formed during interphase, and that a close relationship exists between chromatin and the membranous part of the nuclear pore complex.Octagonality of the nuclear pore complex has been confirmed by a variety of techniques. Using the freeze-etching technique, it was possible to show that the membranous part of the pore complex has an eight-sided outline in human melanoma cells in vitro. Fibers which traverse the pore proper at its corners are continuous and indistinguishable from chromatin at the nucleoplasmic side, as seen in conventionally fixed and sectioned material. Chromatin can be seen in octagonal outline if serial sections are analyzed which are parallel but do not include nuclear membranes (Fig. 1). It is concluded that the shape of the pore rim is due to fibrous material traversing the pore, and may not have any functional significance. In many pores one can recognize a central ring with eight fibers radiating to the corners of the pore rim. Such a structural arrangement is also found to connect eight ribosomes at the nuclear membrane.

Structure, assembly and interactions of the nuclear lamina and the nuclear pore complex

1992 ◽  
Vol 50 (1) ◽  
pp. 490-491
Author(s):  
N. Panté ◽  
M. Jarnik ◽  
E. Heitlinger ◽  
U. Aebi
Keyword(s):  
Nuclear Pore Complex ◽  
Divalent Cations ◽  
Nuclear Lamina ◽  
Dynamic Structure ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Cytoplasmic Filaments ◽  
Radial Spokes ◽  
Nuclear Ring ◽  
Central Plug

The nuclear pore complex (NPC) is a ∼120 MD supramolecular machine implicated in nucleocytoplasmic transport, that is embedded in the double-membraned nuclear envelope (NE). The basic framework of the ∼120 nm diameter NPC consists of a 32 MD cytoplasmic ring, a 66 MD ‘plug-spoke’ assembly, and a 21 MD nuclear ring. The ‘central plug’ seen in en face views of the NPC reveals a rather variable appearance indicating that it is a dynamic structure. Projecting from the cytoplasmic ring are 8 short, twisted filaments (Fig. 1a), whereas the nuclear ring is topped with a ‘fishtrap’ made of 8 thin filaments that join distally to form a fragile, 30-50 nm distal diameter ring centered above the NPC proper (Fig. 1b). While the cytoplasmic filaments are sensitive to proteases, they as well as the nuclear fishtraps are resistant to RNase treatment. Removal of divalent cations destabilizes the distal rings and thereby opens the fishtraps, addition causes them to reform. Protruding from the tips of the radial spokes into perinuclear space are ‘knobs’ that might represent the large lumenal domain of gp210, a membrane-spanning glycoprotein (Fig. 1c) which, in turn, may play a topogenic role in membrane folding and/or act as a membrane-anchoring site for the NPC. The lectin wheat germ agglutinin (WGA) which is known to recognize the ‘nucleoporins’, a family of glycoproteins having O-linked N-acetyl-glucosamine, is found in two locations on the NPC (Fig. 1. d-f): (i) whereas the cytoplasmic filaments appear unlabelled (Fig. 1d&e), WGA-gold labels sites between the central plug and the cytoplasmic ring (Fig. le; i.e., at a radius of 25-35 nm), and (ii) it decorates the distal ring of the nuclear fishtraps (Fig. 1, d&f; arrowheads).

Centromere assembly and non-random sister chromatid segregation in stem cells

2020 ◽  
Vol 64 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Ben L. Carty ◽  
Elaine M. Dunleavy
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Sister Chromatid ◽  
Asymmetric Cell Division ◽  
Protein A ◽  
Germline Stem Cells ◽  
Sister Chromatids ◽  
Centromere Protein A ◽  
Oocyte Meiosis

Abstract Asymmetric cell division (ACD) produces daughter cells with separate distinct cell fates and is critical for the development and regulation of multicellular organisms. Epigenetic mechanisms are key players in cell fate determination. Centromeres, epigenetically specified loci defined by the presence of the histone H3-variant, centromere protein A (CENP-A), are essential for chromosome segregation at cell division. ACDs in stem cells and in oocyte meiosis have been proposed to be reliant on centromere integrity for the regulation of the non-random segregation of chromosomes. It has recently been shown that CENP-A is asymmetrically distributed between the centromeres of sister chromatids in male and female Drosophila germline stem cells (GSCs), with more CENP-A on sister chromatids to be segregated to the GSC. This imbalance in centromere strength correlates with the temporal and asymmetric assembly of the mitotic spindle and potentially orientates the cell to allow for biased sister chromatid retention in stem cells. In this essay, we discuss the recent evidence for asymmetric sister centromeres in stem cells. Thereafter, we discuss mechanistic avenues to establish this sister centromere asymmetry and how it ultimately might influence cell fate.

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