scholarly journals Role of Survivin in cytokinesis revealed by a separation-of-function allele

2011 ◽  
Vol 22 (20) ◽  
pp. 3779-3790 ◽  
Author(s):  
Edith Szafer-Glusman ◽  
Margaret T. Fuller ◽  
Maria Grazia Giansanti
Keyword(s):  
Myosin Ii ◽  
Cell Cortex ◽  
Direct Role ◽  
Central Spindle ◽  
Ring Assembly ◽  
Chromosomal Passenger ◽  
Missense Allele ◽  
Ring Analysis ◽  
And Function

The chromosomal passenger complex (CPC), containing Aurora B kinase, Inner Centromere Protein, Survivin, and Borealin, regulates chromosome condensation and interaction between kinetochores and microtubules at metaphase, then relocalizes to midzone microtubules at anaphase and regulates central spindle organization and cytokinesis. However, the precise role(s) played by the CPC in anaphase have been obscured by its prior functions in metaphase. Here we identify a missense allele of Drosophila Survivin that allows CPC localization and function during metaphase but not cytokinesis. Analysis of mutant cells showed that Survivin is essential to target the CPC and the mitotic kinesin-like protein 1 orthologue Pavarotti (Pav) to the central spindle and equatorial cell cortex during anaphase in both larval neuroblasts and spermatocytes. Survivin also enabled localization of Polo kinase and Rho at the equatorial cortex in spermatocytes, critical for contractile ring assembly. In neuroblasts, in contrast, Survivin function was not required for localization of Rho, Polo, or Myosin II to a broad equatorial cortical band but was required for Myosin II to transition to a compact, fully constricted ring. Analysis of this “separation-of-function” allele demonstrates the direct role of Survivin and the CPC in cytokinesis and highlights striking differences in regulation of cytokinesis in different cell systems.

scholarly journals An ECT2–centralspindlin complex regulates the localization and function of RhoA

2005 ◽  
Vol 170 (4) ◽  
pp. 571-582 ◽  
Author(s):  
Özlem Yüce ◽  
Alisa Piekny ◽  
Michael Glotzer
Keyword(s):  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Myosin Ii ◽  
Cell Cortex ◽  
Contractile Ring ◽  
Division Plane ◽  
Central Spindle ◽  
Ring Assembly ◽  
Cortical Localization ◽  
And Function

In anaphase, the spindle dictates the site of contractile ring assembly. Assembly and ingression of the contractile ring involves activation of myosin-II and actin polymerization, which are triggered by the GTPase RhoA. In many cells, the central spindle affects division plane positioning via unknown molecular mechanisms. Here, we dissect furrow formation in human cells and show that the RhoGEF ECT2 is required for cortical localization of RhoA and contractile ring assembly. ECT2 concentrates on the central spindle by binding to centralspindlin. Depletion of the centralspindlin component MKLP1 prevents central spindle localization of ECT2; however, RhoA, F-actin, and myosin still accumulate on the equatorial cell cortex. Depletion of the other centralspindlin component, CYK-4/MgcRacGAP, prevents cortical accumulation of RhoA, F-actin, and myosin. CYK-4 and ECT2 interact, and this interaction is cell cycle regulated via ECT2 phosphorylation. Thus, central spindle localization of ECT2 assists division plane positioning and the CYK-4 subunit of centralspindlin acts upstream of RhoA to promote furrow assembly.

scholarly journals The Intricate Role of p53 in Adipocyte Differentiation and Function

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2621
Author(s):  
Yun Kyung Lee ◽  
Yu Seong Chung ◽  
Ji Hye Lee ◽  
Jin Mi Chun ◽  
Jun Hong Park
Keyword(s):  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Metabolic Stress ◽  
Health Concern ◽  
Metabolic Dysfunction ◽  
Direct Role ◽  
Proliferation And Apoptosis ◽  
Response To Stress ◽  
And Function

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

scholarly journals The Multiple Roles of Cyk1p in the Assembly and Function of the Actomyosin Ring in Budding Yeast

1999 ◽  
Vol 10 (2) ◽  
pp. 283-296 ◽  
Author(s):  
Katie B. Shannon ◽  
Rong Li
Keyword(s):  
Actin Filaments ◽  
Fluorescent Protein ◽  
Budding Yeast ◽  
Dependent Manner ◽  
Size Change ◽  
Direct Role ◽  
Dynamic Component ◽  
Amino Terminal ◽  
Ring Assembly

The budding yeast IQGAP-like protein Cyk1p/Iqg1p localizes to the mother-bud junction during anaphase and has been shown to be required for the completion of cytokinesis. In this study, video microscopy analysis of cells expressing green fluorescent protein-tagged Cyk1p/Iqg1p demonstrates that Cyk1p/Iqg1p is a dynamic component of the contractile ring during cytokinesis. Furthermore, in the absence of Cyk1p/Iqg1p, myosin II fails to undergo the contraction-like size change at the end of mitosis. To understand the mechanistic role of Cyk1p/Iqg1p in actomyosin ring assembly and dynamics, we have investigated the role of the structural domains that Cyk1p/Iqg1p shares with IQGAPs. An amino terminal portion containing the calponin homology domain binds to actin filaments and is required for the assembly of actin filaments to the ring. This result supports the hypothesis that Cyk1p/Iqg1p plays a direct role in F-actin recruitment. Deletion of the domain harboring the eight IQ motifs abolishes the localization of Cyk1p/Iqg1p to the bud neck, suggesting that Cyk1p/Iqg1p may be localized through interactions with a calmodulin-like protein. Interestingly, deletion of the COOH-terminal GTPase-activating protein-related domain does not affect Cyk1p/Iqg1p localization or actin recruitment to the ring but prevents actomyosin ring contraction. In vitro binding experiments show that Cyk1p/Iqg1p binds to calmodulin, Cmd1p, in a calcium-dependent manner, and to Tem1p, a small GTP-binding protein previously found to be required for the completion of anaphase. These results demonstrate the critical function of Cyk1p/Iqg1p in regulating various steps of actomyosin ring assembly and cytokinesis.

scholarly journals A novel coordinated function of Myosin II with GOLPH3 controls centralspindlin localization during cytokinesis in Drosophila

2020 ◽  
Vol 133 (21) ◽  
pp. jcs252965
Author(s):  
Stefano Sechi ◽  
Anna Frappaolo ◽  
Angela Karimpour-Ghahnavieh ◽  
Roberta Fraschini ◽  
Maria Grazia Giansanti
Keyword(s):  
Plasma Membrane ◽  
Heavy Chain ◽  
Light Chain ◽  
Animal Cell ◽  
Myosin Ii ◽  
Contractile Ring ◽  
Ring Assembly ◽  
Missense Allele ◽  
Phosphatidylinositol 4 ◽  
Muscle Myosin

ABSTRACTIn animal cell cytokinesis, interaction of non-muscle myosin II (NMII) with F-actin provides the dominant force for pinching the mother cell into two daughters. Here we demonstrate that celibe (cbe) is a missense allele of zipper, which encodes the Drosophila Myosin heavy chain. Mutation of cbe impairs binding of Zipper protein to the regulatory light chain Spaghetti squash (Sqh). In dividing spermatocytes from cbe males, Sqh fails to concentrate at the equatorial cortex, resulting in thin actomyosin rings that are unable to constrict. We show that cbe mutation impairs localization of the phosphatidylinositol 4-phosphate [PI(4)P]-binding protein Golgi phosphoprotein 3 (GOLPH3, also known as Sauron) and maintenance of centralspindlin at the cell equator of telophase cells. Our results further demonstrate that GOLPH3 protein associates with Sqh and directly binds the centralspindlin subunit Pavarotti. We propose that during cytokinesis, the reciprocal dependence between Myosin and PI(4)P–GOLPH3 regulates centralspindlin stabilization at the invaginating plasma membrane and contractile ring assembly.

Rac1 promotes kidney collecting duct integrity by limiting actomyosin activity

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
Fabian Bock ◽  
Bertha C. Elias ◽  
Xinyu Dong ◽  
Diptiben V. Parekh ◽  
Glenda Mernaugh ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Collecting Duct ◽  
Myosin Ii ◽  
Ureteric Bud ◽  
Epithelial Integrity ◽  
Epithelial Morphology ◽  
Cytoskeletal Regulation ◽  
Intact Kidney ◽  
And Function

A polarized collecting duct (CD), formed from the branching ureteric bud (UB), is a prerequisite for an intact kidney. The small Rho GTPase Rac1 is critical for actin cytoskeletal regulation. We investigated the role of Rac1 in the kidney collecting system by selectively deleting it in mice at the initiation of UB development. The mice exhibited only a mild developmental phenotype; however, with aging, the CD developed a disruption of epithelial integrity and function. Despite intact integrin signaling, Rac1-null CD cells had profound adhesion and polarity abnormalities that were independent of the major downstream Rac1 effector, Pak1. These cells did however have a defect in the WAVE2–Arp2/3 actin nucleation and polymerization apparatus, resulting in actomyosin hyperactivity. The epithelial defects were reversible with direct myosin II inhibition. Furthermore, Rac1 controlled lateral membrane height and overall epithelial morphology by maintaining lateral F-actin and restricting actomyosin. Thus, Rac1 promotes CD epithelial integrity and morphology by restricting actomyosin via Arp2/3-dependent cytoskeletal branching.

scholarly journals Role of Tropomyosin in Formin-mediated Contractile Ring Assembly in Fission Yeast

2009 ◽  
Vol 20 (8) ◽  
pp. 2160-2173 ◽  
Author(s):  
Colleen T. Skau ◽  
Erin M. Neidt ◽  
David R. Kovar
Keyword(s):  
Fission Yeast ◽  
Actin Filament ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Actin Assembly ◽  
Animal Cells ◽  
Contractile Ring ◽  
Direct Role ◽  
Ring Assembly

Like animal cells, fission yeast divides by assembling actin filaments into a contractile ring. In addition to formin Cdc12p and profilin, the single tropomyosin isoform SpTm is required for contractile ring assembly. Cdc12p nucleates actin filaments and remains processively associated with the elongating barbed end while driving the addition of profilin-actin. SpTm is thought to stabilize mature filaments, but it is not known how SpTm localizes to the contractile ring and whether SpTm plays a direct role in Cdc12p-mediated actin polymerization. Using “bulk” and single actin filament assays, we discovered that Cdc12p can recruit SpTm to actin filaments and that SpTm has diverse effects on Cdc12p-mediated actin assembly. On its own, SpTm inhibits actin filament elongation and depolymerization. However, Cdc12p completely overcomes the combined inhibition of actin nucleation and barbed end elongation by profilin and SpTm. Furthermore, SpTm increases the length of Cdc12p-nucleated actin filaments by enhancing the elongation rate twofold and by allowing them to anneal end to end. In contrast, SpTm ultimately turns off Cdc12p-mediated elongation by “trapping” Cdc12p within annealed filaments or by dissociating Cdc12p from the barbed end. Therefore, SpTm makes multiple contributions to contractile ring assembly during and after actin polymerization.

scholarly journals Analysis of the role of Ser1/Ser2/Thr9 phosphorylation on myosin II assembly and function in live cells

2011 ◽  
Vol 12 (1) ◽  
pp. 52 ◽  
Author(s):  
Jordan R Beach ◽  
Lucila S Licate ◽  
James F Crish ◽  
Thomas T Egelhoff
Keyword(s):  
Myosin Ii ◽  
Live Cells ◽  
And Function

scholarly journals BKCa (Slo) Channel Regulates Mitochondrial Function and Lifespan in Drosophila melanogaster

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 945 ◽  
Author(s):  
Shubha Gururaja Rao ◽  
Piotr Bednarczyk ◽  
Atif Towheed ◽  
Kajol Shah ◽  
Priyanka Karekar ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Mitochondrial Function ◽  
Physiological Role ◽  
Oxygen Species ◽  
Organ Protection ◽  
Bkca Channels ◽  
Direct Role ◽  
Mitochondrial Structure ◽  
And Function

BKCa channels, originally discovered in Drosophila melanogaster as slowpoke (slo), are recognized for their roles in cellular and organ physiology. Pharmacological approaches implicated BKCa channels in cellular and organ protection possibly for their ability to modulate mitochondrial function. However, the direct role of BKCa channels in regulating mitochondrial structure and function is not deciphered. Here, we demonstrate that BKCa channels are present in fly mitochondria, and slo mutants show structural and functional defects in mitochondria. slo mutants display an increase in reactive oxygen species and the modulation of ROS affected their survival. We also found that the absence of BKCa channels reduced the lifespan of Drosophila, and overexpression of human BKCa channels in flies extends life span in males. Our study establishes the presence of BKCa channels in mitochondria of Drosophila and ascertains its novel physiological role in regulating mitochondrial structural and functional integrity, and lifespan.

scholarly journals STAT6 Is Critical for the Induction of Regulatory T Cells In Vivo Controlling the Initial Steps of Colitis-Associated Cancer

2021 ◽  
Vol 22 (8) ◽  
pp. 4049
Author(s):  
Yael Delgado-Ramirez ◽  
Angel Ocaña-Soriano ◽  
Yadira Ledesma-Soto ◽  
Jonadab E. Olguín ◽  
Joselín Hernandez-Ruiz ◽  
...  
Keyword(s):  
Treg Cells ◽  
Tumor Formation ◽  
Mucosal Inflammation ◽  
Direct Role ◽  
Early Stages ◽  
Main Driver ◽  
Induce Resistance ◽  
And Function

Inflammation is the main driver of the tumor initiation and progression in colitis-associated colorectal cancer (CAC). Recent findings have indicated that the signal transducer and activator of transcription 6 (STAT6) plays a fundamental role in the early stages of CAC, and STAT6 knockout (STAT6−/−) mice are highly resistant to CAC development. Regulatory T (Treg) cells play a major role in coordinating immunomodulation in cancer; however, the role of STAT6 in the induction and function of Treg cells is poorly understood. To clarify the contribution of STAT6 to CAC, STAT6−/− and wild type (WT) mice were subjected to an AOM/DSS regimen, and the frequency of peripheral and local Treg cells was determined during the progression of CAC. When STAT6 was lacking, a remarkable reduction in tumor growth was observed, which was associated with decreased inflammation and an increased number of CD4+CD25+Foxp3+ cells in the colon, circulation, and spleen, including an over-expression of TGF-beta, IL-10, and Foxp3, compared to WT mice, during the early stages of CAC development. Conversely, WT mice showed an inverse frequency of Treg cells compared with STAT6−/− mice, which was followed by intestinal tumor formation. Increased mucosal inflammation, histological damage, and tumorigenesis were restored to levels observed in WT mice when an early inhibition/depletion of Treg cells was performed in STAT6−/− mice. Thus, with STAT6 deficiency, an increased number of Treg cells induce resistance against tumorigenesis, arresting tumor-promoting inflammation. We reported a direct role of STAT6 in the induction and function of Treg cells during CAC development and suggest that STAT6 is a potential target for the modulation of immune response in colitis and CAC.

scholarly journals Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2

2015 ◽  
Vol 35 (23) ◽  
pp. 3934-3944 ◽  
Author(s):  
Kayla A. Martin ◽  
Matteo Cesaroni ◽  
Michael F. Denny ◽  
Lena N. Lupey ◽  
Italo Tempera
Keyword(s):  
Gene Expression ◽  
Gene Silencing ◽  
Posttranslational Modifications ◽  
Target Genes ◽  
Global Gene Expression ◽  
Parp Inhibition ◽  
Direct Role ◽  
Polycomb Repressive Complex 2 ◽  
And Function

Posttranslational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of the genes expressed. Gene ontology analysis revealed that PARP could exert these effects through transcription factors and chromatin-remodeling enzymes, including the polycomb repressive complex 2 (PRC2) member EZH2. EZH2 mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a modification associated with chromatin compaction and gene silencing. Both pharmacological inhibition of PARP and knockdown of PARP1 induced the expression of EZH2, which resulted in increased global H3K27me3. Chromatin immunoprecipitation confirmed that PARP1 inhibition led to H3K27me3 deposition at EZH2 target genes, which resulted in gene silencing. Moreover, increased EZH2 expression is attributed to the loss of the occupancy of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition. Together, these data show that PARP plays an important role in global gene regulation and identifies for the first time a direct role of PARP1 in regulating the expression and function of EZH2.

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