The Scribble–Dlg–Lgl Module in Cell Polarity Regulation

Humbert, Patrick O.; Russell, Sarah M.; Smith, Lorey; Richardson, Helena E.

doi:10.1007/978-3-319-14463-4_4

Cited by 15 publications

(39 citation statements)

References 273 publications

(337 reference statements)

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“…Flamingo (Fmi, vertebrate Celsr) associates with both complexes and serves to connect adjacent cells via homophilic interactions. Apicobasal polarity feeds into PCP, as members of the Scribble and Par complex physically bind core PCP components (Humbert et al, 2015;Wu and Mlodzik, 2009). For instance, Scribble stabilizes proximal Vangl localization.…”

Section: Planar Cell Polaritymentioning

confidence: 99%

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Development and dynamics of cell polarity at a glance

Campanale

Sun

Montell

2017

Journal of Cell Science

179

162

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Cells exhibit morphological and molecular asymmetries that are broadly categorized as cell polarity. The cell polarity established in early embryos prefigures the macroscopic anatomical asymmetries characteristic of adult animals. For example, eggs and early embryos have polarized distributions of RNAs and proteins that generate global anterior/posterior and dorsal/ventral axes. The molecular programs that polarize embryos are subsequently reused in multiple contexts. Epithelial cells require apical/basal polarity to establish their barrier function. Migrating cells polarize in the direction of movement, creating distinct leading and trailing structures. Asymmetrically dividing stem cells partition different molecules between themselves and their daughter cells. Cell polarity can develop de novo, be maintained through rounds of cell division and be dynamically remodeled. In this Cell Science at a Glance review and poster, we describe molecular asymmetries that underlie cell polarity in several cellular contexts. We highlight multiple developmental systems that first establish cell/developmental polarity, and then maintain it. Our poster showcases repeated use of the Par, Scribble and Crumbs polarity complexes, which drive the development of cell polarity in many cell types and organisms. We then briefly discuss the diverse and dynamic changes in cell polarity that occur during cell migration, asymmetric cell division and in planar polarized tissues.

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Section: Planar Cell Polaritymentioning

confidence: 99%

“…For instance, Scribble stabilizes proximal Vangl localization. Scrib mutants display PCP defects in diverse tissues, including in mouse neural tube and lung, Drosophila larval eye and wing discs, and impaired wound healing in mammalian skin (Humbert et al, 2015).…”

Section: Planar Cell Polaritymentioning

confidence: 99%

Development and dynamics of cell polarity at a glance

Campanale

Sun

Montell

2017

Journal of Cell Science

179

162

View full text Add to dashboard Cite

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“…In addition, ctenophore species do not have the molecular components to form SJs and lack a Scribble homolog 23, 48 . This suggests that none of the lateral polarity proteins (Dlg, Lgl, and Par-1) can localize to the lateral cortex of the ctenophore cells and explains the cytosolic localization of MlPar-1 during the observed stages 42,45,49,101,102 .…”

Section: Par Protein Asymmetry Is Established Early But Not Maintainementioning

confidence: 93%

“…We have suggested that the polarizing activity of the Par system was already present in epithelial cells of the MRCA between Bilateria and In bilaterians, the mechanism that induces and establishes the asymmetrical localization of Par proteins in the cell cortex during early animal development remains unknown, even though the maintenance of the apicobasal cell polarity in mature epithelial tissue is carried out by a conserved and well-studied mechanism. While the Par/aPKC complex is localized to the apical cortex by its interaction with the CCC and the Crb complex 4,20,23,96,97 , the cortico-lateral localization of Par-1 depends on the stable interaction between SJs and the Scribble complex 20,23, 44,[46][47][48][49]98 . Mutations in any of these components in bilaterian embryos results in a mislocalization of polarity proteins and the disassembling of junctional complexes 4,22,45,46,48,49,[51][52][53] .…”

Section: Par Protein Asymmetry Is Established Early But Not Maintainementioning

confidence: 99%

“…E-cadherin, in turn, sequesters ß-catenin from the cytoplasm that binds to alpha-catenin (forming the Cadherin-Catenin complex; CCC) and links this protein complex to the actin cytoskeleton, thus stabilizing Adherens Junctions (AJs) 1,23,35,[37][38][39][40][41] . The maturation of AJs is essential for the maintenance of the Par/aPKC complex localization at the apical cortex that displaces members of the Scribble complex and Par-1 to basolateral localizations associated with Septate Junctions (SJs) 23, [42][43][44][45][46][47][48][49][50] . Therefore, the regulation of AJs is critical for the maintenance of epithelial polarity and its functional regulation of epithelial physiology 21,22,36,[51][52][53] .…”

Section: Introductionmentioning

confidence: 99%

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Par protein localization during the early development ofMnemiopsis leidyisuggests different modes of epithelial organization in Metazoa

Salinas‐Saavedra

Martindale

2018

Preprint

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In bilaterians and cnidarians, embryonic and epithelial cell-polarity are regulated by the interactions between Par proteins, Wnt/PCP signaling pathway, and cell-cell adhesion. Par proteins are highly conserved across Metazoa, including ctenophores. But strikingly, ctenophore genomes lack components of the Wnt/PCP pathway and cell-cell adhesion complexes; raising the question if ctenophore cells are polarized by mechanisms involving Par proteins. Here, by using immunohistochemistry and live-cell imaging overexpression of specific mRNAs, we describe for the first time the subcellular localization of selected Par proteins in blastomeres and epithelial cells during the embryogenesis of the ctenophore Mnemiopsis leidyi. We show that these proteins distribute differently compared to what has been described for other animals, even though they segregate in a host-specific fashion when expressed in cnidarian embryos. This differential localization might be related to the emergence of different junctional complexes during metazoan evolution. Data obtained here challenge the ancestry of the apicobasal cell polarity and raise questions about the homology of epithelial tissue across the Metazoa. 0

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Drosophila Models of Cell Polarity and Cell Competition in Tumourigenesis

Fahey-Lozano¹,

Marca²,

Portela³

et al. 2019

Advances in Experimental Medicine and Biology

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Cell competition is an important surveillance mechanism that measures relative fitness between cells in a tissue during development, homeostasis, and disease. Specifically, cells that are "less fit" (losers) are actively eliminated by relatively "more fit" (winners) neighbours, despite the less fit cells otherwise being able to survive in a genetically uniform tissue. Originally described in the epithelial tissues of Drosophila larval imaginal discs, cell competition has since been shown to occur in other epithelial and non-epithelial Drosophila tissues, as well as in mammalian model systems. Many genes and signalling pathways have been identified as playing conserved roles in the mechanisms of cell competition.Among them are genes required for the establishment and maintenance of apico-basal cell polarity: the Crumbs/Stardust/Patj (Crb/Sdt/Patj), Bazooka/Par-6/atypical Protein Kinase C (Baz/Par-6/aPKC), and Scribbled/Discs large 1/Lethal (2) giant larvae (Scrib/Dlg1/L(2)gl) modules. In this chapter, we describe the concepts and mechanisms of cell competition, with emphasis on the relationship between cell polarity proteins and cell competition, particularly the Scrib/Dlg1/L(2)gl module, since this is the best described module in this emerging field. Cell competitionCell competition can be described as a biological surveillance mechanism, conserved from Drosophila to mammals, that allows cells to sense each other's relative fitness levels and actively eliminate the ones that are "less fit" (Baker, 2017;Clavería & Torres, 2016;Madan et al, 2018). These less fit cells are commonly referred to as "loser cells", while the "more fit" cells that remain in the tissue are called "winner cells" (Figure 1A). A key aspect of cell competition interactions is that they are context dependent -this means that loser cells, if present in a genetically homogeneous tissue, proliferate and survive (Figure 1B). This indicates these cells do not possess an intrinsic propensity to die -only within a mosaic tissue are they recognised and actively eliminated by more fit cells. Broadly, there are two distinct types of cell competition: 1) elimination of cells due to acquired characteristics that render them less fit, and 2) elimination by cells due to acquired characteristics that render them more fit (a.k.a."super-competition"). In the first scenario, cell competition is thought be important for preventing disease by allowing correct tissue and organ development, maintaining tissue homeostasis, or delaying aging, since it promotes the survival of the best quality cells while eliminating those that could be harmful for the individual (Merino et al, 2016;Merino et al, 2015). In the second case, "super-fit" mutant cells are capable of eliminating perfectly healthy wild-type cells (Figure 1C). This form of cell competition is thought to be related to the progression of diseases such as cancer.Cell competition was first described four decades ago in Drosophila wing imaginal discs (Morata & Ripoll, 1975). It was observed that cells heterozygou...

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The Scribble–Dlg–Lgl Module in Cell Polarity Regulation

Cited by 15 publications

References 273 publications

Development and dynamics of cell polarity at a glance

Development and dynamics of cell polarity at a glance

Par protein localization during the early development ofMnemiopsis leidyisuggests different modes of epithelial organization in Metazoa

Drosophila Models of Cell Polarity and Cell Competition in Tumourigenesis

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