Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos

Etemad-Moghadam, Bijan; Guo, Su; Kemphues, Kenneth J.

doi:10.1016/0092-8674(95)90187-6

Cited by 393 publications

(316 citation statements)

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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).…”

Section: Rnai Clone Genementioning

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.…”

mentioning

confidence: 99%

“…anterior PARs) proteins are localized at the anterior cortex of the embryo (Etemad-Moghadam et al 1995;Tabuse et al 1998;Hung and Kemphues 1999), while PAR-1 and PAR-2 are restricted to the posterior cortex Boyd et al 1996). 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).…”

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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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Section: Rnai Clone Genementioning

confidence: 99%

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confidence: 99%

mentioning

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 products of the Par genes are quite diverse in function. Par-1 and Par-4 encode serine/threonine-directed protein kinases Watts et al 2000); Par-2 is a RING finger domain protein that may function as an E3 ubiquitin ligase (Levitan et al 1994); Par-3 and Par-6 are PDZ (PSD95/Dlg/ZO1) domain-containing proteins with scaffolding or adaptor functions (Etemad-Moghadam et al 1995;Hung and Kemphues 1999); Par-5 is a 14-3-3 protein that binds to phosphorylated serine and threonine residues (Morton et al 2002); and PKC-3 is an atypical protein kinase C (aPKC). With the exception of Par-2, all of the Par proteins and aPKC are conserved throughout the Metazoa.…”

Section: Par Proteins: Interpreters Of Cell Polaritymentioning

confidence: 99%

Widely Conserved Signaling Pathways in the Establishment of Cell Polarity

McCaffrey

Macara

2009

Cold Spring Harbor Perspectives in Biology

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“…Axis of polarity absence of PAR-2, PAR-3 covers the entire cortex, whereas in absence of PAR-3, PAR-2 localizes uniformly [9,11]. PAR proteins exert their spindle-positioning function by controlling MT-cortex interactions.…”

Section: (A) (B)mentioning

confidence: 99%

Spindle asymmetry: a compass for the cell

Kusch¹,

Liakopoulos²,

Barral³

2003

Trends in Cell Biology

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Spatial coordination of the cell-division axis with cellular polarity and/or with the position of neighboring cells is crucial for embryonic development, organogenesis and tissue homeostasis. In most cell types, the position of the mitotic spindle at the onset of anaphase dictates the orientation of the division axis; in unicellular organisms, it plays an important role in chromosome segregation. Cortical factors play a key role in the orientation of the spindle. Recent data from yeast reveal that the spindle does not passively react to cortical signals but actively interprets them to find its correct position. We review the data leading to a 'compass model' for spindle positioning and discuss its potential generality.During cell division, the position of the spindle within the cell dictates whether polarized factors become symmetrically or asymmetrically segregated between daughter cells (Figure 1). In many cell types, polarized factors comprise cell-fate determinants. Asymmetric segregation of these factors is an important mechanism for the generation of cell diversity in multi and unicellular organisms. Misorientation of the spindle severely impairs the segregation of fate determinants and hence development.During spindle positioning, spindle rotation ensures the targeting of the two centrosomes to opposite ends of the cell and thereby the alignment of the spindle with the axis of polarity (Box 1). Other spindle movements include displacement towards the edge of the cell, leading to different sizes of the daughter cells. Here, we focus on the mechanisms of spindle alignment. Using Drosophila melanogaster and Caenorhabditis elegans as models, many laboratories have identified several factors involved in this process. These factors provide cortical cues to orientate the spindle, participate in the cortical capture and/or pulling of astral microtubules (MTs) and govern the movement of spindle poles within the cell. How this leads to differential positioning of centrosomes to different cellends is unclear. Data from budding yeast indicate that, depending on the spindle pole from which they emanate, astral MTs have distinct abilities to interact with different cortical sites. This suggests that the asymmetry of the mitotic spindle is a prerequisite for the interpretation of cortical polarity by the spindle. Here, we review the yeast data implicating spindle asymmetry in spindle orientation.The possibility that related mechanisms are also used in higher eukaryotes are also discussed.Spindle positioning: the role of the cortex Model organisms are powerful tools to study the role of cortical polarity in spindle movements during development. During the first division of the C. elegans embryo, the mitotic spindle aligns with the anterio -posterior axis of the oocyte. A rotation by 908 that occurs in the resulting posterior cell reorientates the spindle along the anterioposterior axis of the embryo [1][2][3]. Groundbreaking experiments by Tony Hyman established that, in C. elegans, interaction of astral MTs with the cor...

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Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos

Cited by 393 publications

References 40 publications

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

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

Widely Conserved Signaling Pathways in the Establishment of Cell Polarity

Spindle asymmetry: a compass for the cell

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