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[
Trends in Cell Biology,
1997]
Antisense knockout techniques are also being used in worm embryos to inactivate transcripts and look at the effects. This method was pioneered by Su Guo and Ken Kemphues in 1995, initially to verify that the clone they had isolated corresponded to the
par-1 gene, and now has been used by a large number of groups studying a variety of different genes.
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Parasitology,
2007]
Signal transduction molecules play key roles in the regulation of developmental processes, such as morphogenesis, organogenesis and cell differentiation in all organisms. They are organized into ''pathways'' that represent a coordinated network of cell-surface receptors and intracellular molecules, being involved in sensing environmental stimuli and transducing signals to regulate or modulate cellular processes, such as gene expression and cytoskeletal dynamics. A particularly important group of molecules implicated in the regulation of the cytoskeleton for the establishment and maintenance of cell polarity is the PAR proteins (derived from partition defective in asymmetric cell division). The present article reviews salient aspects of PAR proteins involved in the early embryonic development and morphogenesis of the free-living nematode Caenorhabditis elegans and some other organisms, with an emphasis on the molecule PAR-1. Recent advances in the knowledge and understanding of PAR-1 homologues from the economically important parasitic nematode, Haemonchus contortus, of small ruminants is summarized and discussed in the context of exploring avenues for future research in this area for parasitic nematodes.
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Curr Biol,
2002]
Six par genes (
par-1 through
par-6) have been identified in Caenorhabditis elegans. Loss-of-function mutations in any par locus results in loss of anterior-posterior (AP) asymmetries during the first two embryonic cell divisions. This results in a failure to restrict developmental regulators to specific embryonic cells, mitotic spindle orientation defects and abnormal cell fate pattering. In sum, the par genes appear responsible for establishing asymmetries that define the AP body axis in C. elegans.
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F1000Res,
2017]
The scaffold protein Par-3 ( Drosophila Bazooka) is a central organizer of cell polarity across animals. This review focuses on how the clustering of Par-3 contributes to cell polarity. It begins with the Par-3 homo-oligomerization mechanism and its regulation by Par-1 phosphorylation. The role of polarized cytoskeletal networks in distributing Par-3 clusters to one end of the cell is then discussed, as is the subsequent maintenance of polarized Par-3 clusters through hindered mobility and inhibition from the opposite pole. Finally, specific roles of Par-3 clusters are reviewed, including the bundling of microtubules, the cortical docking of centrosomes, the growth and positioning of cadherin-catenin clusters, and the inhibition of the Par-6-aPKC kinase cassette. Examples are drawn from Drosophila, Caenorhabditis elegans, mammalian cell culture, and biochemical studies.
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Dev Cell,
2007]
The par genes were discovered in genetic screens for regulators of cytoplasmic partitioning in the early embryo of C. elegans, and encode six different proteins required for asymmetric cell division by the worm zygote. Some of the PAR proteins are localized asymmetrically and form physical complexes with one another. Strikingly, the PAR proteins have been found to regulate cell polarization in many different contexts in diverse animals, suggesting they form part of an ancient and fundamental mechanism for cell polarization. Although the picture of how the PAR proteins function remains incomplete, cell biology and biochemistry are beginning to explain how PAR proteins polarize cells.
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Science,
2002]
The eggs of Caenorhabditis elegans and Drosophila bear little similarity to each other, yet both depend on the par genes for control of anterior-posterior polarity. Here we explore possible common roles for the par genes (pars) in converting transient asymmetries into stably polarized axes. Although clear mechanistic parallels remain to be established, par-dependent regulation of microtubule dynamics and protein stability emerge as common themes.
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Development,
2011]
Cell polarity is essential for cells to divide asymmetrically, form spatially restricted subcellular structures and participate in three-dimensional multicellular organization. PAR proteins are conserved polarity regulators that function by generating cortical landmarks that establish dynamic asymmetries in the distribution of effector proteins. Here, we review recent findings on the role of PAR proteins in cell polarity in C. elegans and Drosophila, and emphasize the links that exist between PAR networks and cytoskeletal proteins that both regulate PAR protein localization and act as downstream effectors to elaborate polarity within the cell.
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FEBS J,
2021]
The Par-3/Baz family of polarity determinants is highly conserved across metazoans, and includes C. elegans PAR-3, Drosophila Bazooka (Baz), human Par-3 (PARD3) and human Par-3-like (PARD3B). The C. elegans PAR-3 protein localises to the anterior pole of asymmetrically dividing zygotes with CDC42, atypical protein kinase C (aPKC) and PAR-6. The same C. elegans 'PAR complex' can also localise in an apical ring in epithelial cells. Drosophila Baz localises to the apical pole of asymmetrically dividing neuroblasts with Cdc42-aPKC-Par-6, while in epithelial cells localises both in an apical ring with Cdc42-aPKC-Par6 as well as with E-cadherin at adherens junctions. These apical and junctional localisations have become separated in human PARD3, which is strictly apical in many epithelia, and human PARD3B, which is strictly junctional in many epithelia. We discuss the molecular basis for this fundamental difference in localisation, as well as the possible functions of Par-3/Baz family proteins as oligomeric clustering agents at the apical domain or at adherens junctions in epithelial stem cells. The evolution of Par-3 family proteins into distinct apical PARD3 and junctional PARD3B orthologs coincides with the emergence of stratified squamous epithelia in vertebrates, where PARD3B, but not PARD3, is strongly expressed in basal layer stem cells - which lack a typical apical domain. We speculate that PARD3B may contribute to clustering of E-cadherin, signalling from adherens junctions via Src family kinases, or mitotic spindle orientation by adherens junctions in response to mechanical forces.
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Philos Trans R Soc Lond B Biol Sci,
2013]
The PAR clan of polarity regulating genes was initially discovered in a genetic screen searching for genes involved in asymmetric cell divisions in the Caenorhabditis elegans embryo. Today, investigations in worms, flies and mammals have established PAR proteins as conserved and fundamental regulators of animal cell polarization in a broad range of biological phenomena requiring cellular asymmetries. The human homologue of invertebrate PAR-4, a serine-threonine kinase LKB1/STK11, has caught attention as a gene behind Peutz-Jeghers polyposis syndrome and as a bona fide tumour suppressor gene commonly mutated in sporadic cancer. LKB1 functions as a master regulator of AMP-activated protein kinase (AMPK) and 12 other kinases referred to as the AMPK-related kinases, including four human homologues of PAR-1. The role of LKB1 as part of the energy sensing LKB1-AMPK module has been intensively studied, whereas the polarity function of LKB1, in the context of homoeostasis or cancer, has gained less attention. Here, we focus on the PAR-4 identity of LKB1, discussing the weight of evidence indicating a role for LKB1 in regulation of cell polarity and epithelial integrity across species and highlight recent investigations providing new insight into the old question: does the PAR-4 identity of LKB1 matter in cancer?
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[
Cell,
2000]
Current understanding of the way in which embryonic polarity is established relies heavily on studies of maternal effect lethal mutants in D. melanogaster and C. elegans. Although the analysis in worms began in earnest about a decade after the explosion of information from flies, we now know enough about both systems to make comparisons meaningful, and to ask whether there are conserved mechanisms used for establishing embryonic polarity. Thus far, the single common feature is translational repression, which has been shown to localize important fate regulators in both systems. Now, however, in this issue of Cell, Shulman and colleagues report an analysis in D. melanogaster of the first molecule to play an important and perhaps conserved role in both animals, PAR-1.