Dlg, Scribble and Lgl in cell polarity, cell proliferation and cancer

BioEssays ◽  
2003 ◽  
Vol 25 (6) ◽  
pp. 542-553 ◽  
Author(s):  
Patrick Humbert ◽  
Sarah Russell ◽  
Helena Richardson
Keyword(s):  
Cell Proliferation ◽  
Cell Polarity

Cortical Cyclin A controls spindle orientation during asymmetric cell division

2021 ◽  
Author(s):  
Pénélope Darnat ◽  
Angelique Burg ◽  
Jérémy Sallé ◽  
Jérôme Lacoste ◽  
Sophie Louvet-Vallée ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Planar Cell Polarity ◽  
Asymmetric Cell Division ◽  
Cyclin A ◽  
Spindle Orientation ◽  
Posterior Cortex ◽  
Cell Diversity

Abstract Cell proliferation and cell polarity need to be precisely coordinated to orient the asymmetric cell divisions crucial for generating cell diversity in epithelia. In many instances, the Frizzled/Dishevelled planar cell polarity pathway is involved in mitotic spindle orientation, but how this is spatially and temporally coordinated with cell cycle progression has remained elusive. Using Drosophila sensory organ precursor cells as a model system, we show that Cyclin A, the main Cyclin driving the transition to M-phase of the cell cycle, is recruited to the apical-posterior cortex in prophase by the Frizzled/Dishevelled complex. This cortically localized Cyclin A then regulates the orientation of the division by recruiting Mud, a homologue of NuMA, the well-known spindle-associated protein. The observed non-canonical subcellular localization of Cyclin A reveals this mitotic factor as a direct link between cell proliferation, cell polarity and spindle orientation.

scholarly journals Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia

2003 ◽  
Vol 163 (5) ◽  
pp. 1089-1098 ◽  
Author(s):  
Melissa M. Rolls ◽  
Roger Albertson ◽  
Hsin-Pei Shih ◽  
Cheng-Yu Lee ◽  
Chris Q. Doe
Keyword(s):  
Cell Proliferation ◽  
Cell Polarity ◽  
Cell Types ◽  
Proper Function ◽  
Larval Stages ◽  
Kinase C ◽  
Discs Large ◽  
Lethal Giant Larvae ◽  
Cell Diversity ◽  
Apical Localization

Cell polarity is essential for generating cell diversity and for the proper function of most differentiated cell types. In many organisms, cell polarity is regulated by the atypical protein kinase C (aPKC), Bazooka (Baz/Par3), and Par6 proteins. Here, we show that Drosophila aPKC zygotic null mutants survive to mid-larval stages, where they exhibit defects in neuroblast and epithelial cell polarity. Mutant neuroblasts lack apical localization of Par6 and Lgl, and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation. Mutant imaginal disc epithelia have defects in apical/basal cell polarity and tissue morphology. In addition, we show that aPKC mutants show reduced cell proliferation in both neuroblasts and epithelia, the opposite of the lethal giant larvae (lgl) tumor suppressor phenotype, and that reduced aPKC levels strongly suppress most lgl cell polarity and overproliferation phenotypes.

PDZ domains: the building blocks regulating tumorigenesis

2011 ◽  
Vol 439 (2) ◽  
pp. 195-205 ◽  
Author(s):  
Vanitha Krishna Subbaiah ◽  
Christian Kranjec ◽  
Miranda Thomas ◽  
Lawrence Banks
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Cell Polarity ◽  
Pdz Domain ◽  
Building Blocks ◽  
Signal Transduction Pathways ◽  
Pdz Domains ◽  
Binding Motifs ◽  
Cytoskeletal Organization ◽  
Specific Process

Over 250 PDZ (PSD95/Dlg/ZO-1) domain-containing proteins have been described in the human proteome. As many of these possess multiple PDZ domains, the potential combinations of associations with proteins that possess PBMs (PDZ-binding motifs) are vast. However, PDZ domain recognition is a highly specific process, and much less promiscuous than originally thought. Furthermore, a large number of PDZ domain-containing proteins have been linked directly to the control of processes whose loss, or inappropriate activation, contribute to the development of human malignancies. These regulate processes as diverse as cytoskeletal organization, cell polarity, cell proliferation and many signal transduction pathways. In the present review, we discuss how PBM–PDZ recognition and imbalances therein can perturb cellular homoeostasis and ultimately contribute to malignant progression.

scholarly journals Abnormalities in cell proliferation and apico-basal cell polarity are separable in Drosophila lgl mutant clones in the developing eye

2007 ◽  
Vol 311 (1) ◽  
pp. 106-123 ◽  
Author(s):  
Nicola A. Grzeschik ◽  
Nancy Amin ◽  
Julie Secombe ◽  
Anthony M. Brumby ◽  
Helena E. Richardson
Keyword(s):  
Cell Proliferation ◽  
Cell Polarity ◽  
Basal Cell

scholarly journals MST kinases in development and disease

2015 ◽  
Vol 210 (6) ◽  
pp. 871-882 ◽  
Author(s):  
Barry J. Thompson ◽  
Erik Sahai
Keyword(s):  
Cell Proliferation ◽  
Drosophila Melanogaster ◽  
Cell Migration ◽  
Autoimmune Disease ◽  
Cell Polarity ◽  
Signaling Molecules ◽  
Organ Size ◽  
Kinase Family ◽  
And Function ◽  
Related Proteins

The mammalian MST kinase family, which is related to the Hippo kinase in Drosophila melanogaster, includes five related proteins: MST1 (also called STK4), MST2 (also called STK3), MST3 (also called STK24), MST4, and YSK1 (also called STK25 or SOK1). MST kinases are emerging as key signaling molecules that influence cell proliferation, organ size, cell migration, and cell polarity. Here we review the regulation and function of these kinases in normal physiology and pathologies, including cancer, endothelial malformations, and autoimmune disease.

Murine polycystic kidney epithelial cell lines have increased integrin-mediated adhesion to collagen

1994 ◽  
Vol 267 (6) ◽  
pp. F1082-F1093 ◽  
Author(s):  
J. van Adelsberg
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Cell Polarity ◽  
Cell Lines ◽  
Autosomal Recessive ◽  
Polycystic Kidney ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Epithelial Cell Lines ◽  
Cell Matrix Interactions

Polycystic kidney disease (PKD), in which epithelial cysts arise from or instead of normal renal tubules, is one of the most common genetic diseases. It has both autosomal dominant and autosomal recessive inheritance in humans and in experimental animals. Epithelial cells lining the cysts have an increased rate of proliferation, abnormal polarity of Na-K-adenosinetriphosphatase, which is localized to apical and sometimes lateral membrane domains, and an abnormal extracellular matrix. One hypothesis that explains the simultaneous acquisition of these characteristics as the result of several different genetic mutations is that cell-matrix interactions, which are known to regulate cell proliferation and cell polarity, are altered in PKD. I have created immortalized renal epithelial cell lines from C57Bl/6Jcpk mice with PKD, an autosomal recessive trait in these animals, and from their phenotypically normal littermates. Using these cell lines, I show that polycystic cells have increased adhesion to collagens and laminin mediated by an integrin. These results demonstrate that cell-matrix interactions are defective in PKD and suggest that these interactions may be involved in the abnormalities of cell polarity and cell proliferation seen in these disorders.

scholarly journals Sro7 and Sro77, the yeast homologues of the Drosophila lethal giant larvae (Lgl), regulate cell proliferation via the Rho1–Tor1 pathway

Microbiology ◽  
2014 ◽  
Vol 160 (10) ◽  
pp. 2208-2214 ◽  
Author(s):  
Liang-Chun Liou ◽  
Qun Ren ◽  
Qiuqiang Gao ◽  
Zhaojie Zhang
Keyword(s):  
Cell Proliferation ◽  
Cell Polarity ◽  
Smooth Surface ◽  
Colony Growth ◽  
Tumour Suppressor ◽  
Colony Development ◽  
Double Mutation ◽  
Double Deletion ◽  
Transmission Electron ◽  
Lethal Giant Larvae

Saccharomyces cerevisiae Sro7 and Sro77 are homologues of the Drosophila tumour suppressor lethal giant larvae (Lgl), which regulates cell polarity in Drosophila epithelial cells. Here, we showed that double mutation of SRO7/SRO77 was defective in colony growth. The colony of the SRO7/SRO77 double deletion was much smaller than the WT and appeared to be round with a smooth surface, compared with the WT. Analysis using transmission electron microscopy revealed multiple defects of the colony cells, including multiple budding, multiple nuclei, cell lysis and dead cells, suggesting that the double deletion caused defects in cell polarity and cell wall integrity (CWI). Overexpression of RHO1, one of the central regulators of cell polarity and CWI, fully recovered the sro7Δ/sro77Δ phenotype. We further demonstrated that sro7Δ/sro77Δ caused a decrease of the GTP-bound, active Rho1, which in turn caused an upregulation of TOR1. Deletion of TOR1 in sro7Δ/sro77Δ (sro7Δ/sro77Δ/tor1Δ) recovered the cell growth and colony morphology, similar to WT. Our results suggested that the tumour suppressor homologue SRO7/SRO77 regulated cell proliferation and yeast colony development via the Rho1–Tor1 pathway.

Apicobasal polarity and cell proliferation during development

2012 ◽  
Vol 53 ◽  
pp. 95-109 ◽  
Author(s):  
Nitin Sabherwal ◽  
Nancy Papalopulu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Polarity ◽  
Cross Talk ◽  
Polarization State ◽  
Cell Polarization ◽  
Cellular Processes ◽  
Current State ◽  
Apicobasal Polarity ◽  
A Cell

Cell polarization and cell division are two fundamental cellular processes. The mechanisms that establish and maintain cell polarity and the mechanisms by which cells progress through the cell cycle are now fairly well understood following decades of experimental work. There is also increasing evidence that the polarization state of a cell affects its proliferative properties. The challenge now is to understand how these two phenomena are mechanistically connected. The aim of the present chapter is to provide an overview of the evidence of cross-talk between apicobasal polarity and proliferation, and the current state of knowledge of the precise mechanism by which this cross-talk is achieved.

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