Polarization of the<i>C. elegans</i>zygote proceeds via distinct establishment and maintenance phases

Cuenca, Adrian; Schetter, Aaron J.; Aceto, Donato; Kemphues, Kenneth J.; Seydoux, Géraldine

doi:10.1242/dev.00284

Cited by 269 publications

(511 citation statements)

References 34 publications

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“…The independence of NR on RhoA activity is not entirely surprising as recent work links the Cdc42/Par6/PKC complex to the regulated degradation of RhoA during dynamic movements of the plasma membrane (Wang et al, 2003); moreover, MT polarization has previously been shown to be independent of Rho-dependent contractility in other mammalian cells (Omelchenko et al, 2002). The role of Cdc42 in controlling MTOC positioning in Swiss 3T3 fibroblasts concurs with results previously obtained in the nematode C. elegans (Cuenca et al, 2003), astrocytes (Etienne-Manneville andHall, 2001, 2003), and bovine aortic endothelial cells (BAEC; Tzima et al, 2003). Our results, however, seemingly conflict with those obtained by Wojciak-Stothard and Ridley (2003), who showed that MTOC polarization in human umbilical vein endothelial cells (HUVEC) is mediated by Rho and Rac, not Cdc42.…”

Section: Mtoc Repositioning and Nucleus Movement Are Mediated By Cdc42supporting

confidence: 84%

Cdc42 Mediates Nucleus Movement and MTOC Polarization in Swiss 3T3 Fibroblasts under Mechanical Shear Stress

Lee

Chang

Tseng

et al. 2005

MBoC

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Nucleus movement is essential during nucleus positioning for tissue growth and development in eukaryotic cells. However, molecular regulators of nucleus movement in interphase fibroblasts have yet to be identified. Here, we report that nuclei of Swiss 3T3 fibroblasts undergo enhanced movement when subjected to shear flows. Such movement includes both rotation and translocation and is dependent on microtubule, not F-actin, structure. Through inactivation of Rho GTPases, well-known mediators of cytoskeleton reorganization, we demonstrate that Cdc42, not RhoA or Rac1, controls the extent of nucleus translocation, and more importantly, of nucleus rotation in the cytoplasm. In addition to generating nuclei movement, we find that shear flows also causes repositioning of the MTOC in the direction of flow. This behavior is also controlled by Cdc42 via the Par6/protein kinase C pathway. These results are the first to establish Cdc42 as a molecular regulator of not only shear-induced MTOC polarization in Swiss 3T3 fibroblasts, but also of shear-induced microtubule-dependent nucleus movement. We propose that the movements of MTOC and nucleus are coupled chemically, because they are both regulated by Cdc42 and dependent on microtubule structure, and physically, possibly via Hook/SUN family homologues similar to those found in Caenorhabditis elegans. INTRODUCTIONNucleus positioning is an essential process in cell development and plays a major role in mating and mitosis in yeast (Hagan and Yanagida, 1997), asymmetric division of zygotes in Caenorhabditis elegans (Pellettieri and Seydoux, 2002;Tsou et al., 2003), nucleus organization in interphase murine cells (Abney et al., 1997;Cerda et al., 1999), and motility in human neuronal cells (Morris et al., 1998). To adopt its proper cytoplasmic position, the nucleus must migrate to its destination. The molecular mechanisms that drive such nucleus motion have been investigated in lower eukaryotic cells and have been found to be cytoskeleton dependent (Hagan and Yanagida, 1997;Morris et al., 1998;Reinsch and Gonczy, 1998;Morris, 2000). Early studies on 3T3 fibroblasts have shown that intracellular nucleus movement includes rigidbody motion when these cells are subject to shear stimulus and rigid-body nucleus rotation (NR) when treated with the Golgi-perturbing agent monensin (Paddock and Albrecht-Buehler, 1986). However, the molecular mechanisms that coordinate nucleus motion in fibroblasts remain unknown.In Swiss 3T3 fibroblasts, both the actin and microtubule (MT) filament networks play a central role in various cellular functions such as maintaining cell shape and adhesion and orchestrating cell migration and division (Hall, 1998;Lane and Allan, 1998;Omelchenko et al., 2002;Small et al., 2002); however, the involvement of F-actin and MT in nucleus movement in those cells remains unexplored. RhoGTPases RhoA, Rac1, and Cdc42 are known major regulators of the organization of the actin and MT cytoskeletons in Swiss 3T3 fibroblasts (Nobes and Hall, 1995;Hall, 1998;Bishop and Hall, 20...

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Section: Mtoc Repositioning and Nucleus Movement Are Mediated By Cdc42supporting

confidence: 84%

Cdc42 Mediates Nucleus Movement and MTOC Polarization in Swiss 3T3 Fibroblasts under Mechanical Shear Stress

Lee

Chang

Tseng

et al. 2005

MBoC

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“…PAR-3 and PAR-6 localize to the anterior cortex in wild-type embryos (Etemad-Moghadam et al 1995;Hung and Kemphues 1999). In par-2 mutants, polarity cannot be maintained and the anterior PARs expand toward the posterior (Cuenca et al 2003). We observed that PAR-3 and PAR-6 proteins are restricted to the anterior cortex of most nos-3(q650); par-2(it5ts) double-mutant embryos (Figure 2).…”

Section: Rnai Clone Genementioning

confidence: 76%

“…The first division of the embryo is asymmetric, resulting in two cells that are different in size and fate. The seven PAR proteins (PAR-1 to PAR-6 and PKC-3) are found at the cortex of the zygote and are responsible for specifying the anteroposterior axis of polarity (Kemphues and Strome 1997;Tabuse et al 1998;Cuenca et al 2003). Embryos mutant for any par gene do not properly establish polarity, undergo symmetric cell divisions, and fail to hatch.…”

mentioning

confidence: 99%

“…This localization along the antero-posterior axis is mutually exclusive, as members of the anterior and posterior groups show little overlap in their respective localization and the PAR-2 and PAR-3 proteins exclude each other from their respective cortices (Etemad-Moghadam et al 1995;Boyd et al 1996;Cuenca et al 2003). Therefore, PAR proteins define anterior and posterior cortical domains in the zygote and specify cell polarity and asymmetric cell divisions in the early C. elegans embryo.…”

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confidence: 99%

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A Genomewide Screen for Suppressors of par-2 Uncovers Potential Regulators of PAR Protein-Dependent Cell Polarity in Caenorhabditis elegans

Labbé

Pacquelet²,

Marty³

et al. 2006

Genetics

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The PAR proteins play an essential role in establishing and maintaining cell polarity. While their function is conserved across species, little is known about their regulators and effectors. Here we report the identification of 13 potential components of the C. elegans PAR polarity pathway, identified in an RNAi-based, systematic screen to find suppressors of par-2(it5ts) lethality. Most of these genes are conserved in other species. Phenotypic analysis of double-mutant animals revealed that some of the suppressors can suppress lethality associated with the strong loss-of-function allele par-2(lw32), indicating that they might impinge on the PAR pathway independently of the PAR-2 protein. One of these is the gene nos-3, which encodes a homolog of Drosophila Nanos. We find that nos-3 suppresses most of the phenotypes associated with loss of par-2 function, including early cell division defects and maternal-effect sterility. Strikingly, while PAR-1 activity was essential in nos-3; par-2 double mutants, its asymmetric localization at the posterior cortex was not restored, suggesting that the function of PAR-1 is independent of its cortical localization. Taken together, our results identify conserved components that regulate PAR protein function and also suggest a role for NOS-3 in PAR protein-dependent cell polarity.

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“…Ainsi dans un mutant par-2, le complexe antérieur peut s'étendre jusqu'au pôle postérieur et occuper uniformément le cortex ( Figure 1B). Inversement, dans un mutant par-6, le domaine PAR-2 demeure uniforme sur l'intégralité du cortex [6]. Chaque protéine PAR est …”

Section: Découverte Des Protéines Par Dans L'embryon De C Elegansunclassified

Mécanismes de division cellulaire asymétrique

2010

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Polarization of theC. eleganszygote proceeds via distinct establishment and maintenance phases

Cited by 269 publications

References 34 publications

Cdc42 Mediates Nucleus Movement and MTOC Polarization in Swiss 3T3 Fibroblasts under Mechanical Shear Stress

Cdc42 Mediates Nucleus Movement and MTOC Polarization in Swiss 3T3 Fibroblasts under Mechanical Shear Stress

A Genomewide Screen for Suppressors of par-2 Uncovers Potential Regulators of PAR Protein-Dependent Cell Polarity in Caenorhabditis elegans

Mécanismes de division cellulaire asymétrique

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