Disease relevance of Cell Polarity

• Finally, we define roles for the canonical Wingless and Hedgehog pathways and for core planar cell polarity proteins in denticle polarity [1].
• This study has explored one potential aspect of biological tumour heterogeneity within grade by examining the relationship between cell polarity, the cell adhesion molecule E-cadherin, a major effector of cell polarity, and outcome, in 149 grade I infiltrating ductal breast carcinomas [2].
• Pathogenesis of colloid (pure mucinous) carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of colloid carcinoma in the breast and pancreas [3].
• These data demonstrate that the different responses to HGF/SF depend on the state of the epithelial cells: morphogenesis requires epithelial differentiation and cell polarity, whereas metastasis is observed when the cells have lost their epithelial characteristics [4].

High impact information on Cell Polarity

• Defective planar cell polarity in polycystic kidney disease [5].
• Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling [6].
• The apical determinants aPKC and dPatj regulate Frizzled-dependent planar cell polarity in the Drosophila eye [7].
• Cdc42 is a key regulator of cell polarity and actin dynamics [8].
• Thus, neuronal polarity is likely to be controlled by the mPar3/mPar6/aPKC complex and the PI 3-kinase signaling pathway, both serving evolutionarily conserved roles in specifying cell polarity [9].

Biological context of Cell Polarity

• Here we show that Far1p functions in both subcellular compartments: nuclear Far1p is required to arrest the cell cycle, whereas cytoplasmic Far1p is involved in the establishment of cell polarity [10].
• Evolutionarily conserved in eukaryotes, formin homology (FH) proteins, or formins, exert their effects on the actin and microtubule (MT) networks during meiosis, mitosis, the maintenance of cell polarity, vesicular trafficking, signaling to the nucleus and embryonic development [11].
• Members of the FH protein family play essential roles in cytokinesis and in driving alterations in cell polarity [12].
• Phosphoinositide 3-kinase plays a central and possibly pivotal role in establishing and maintaining cell polarity by regulating the subcellular localization and activation of downstream effectors that are essential for regulating cell polarity and proper chemotaxis [13].
• We propose that Crumbs stabilizes the apical SBMS via DMoesin and actin, leading to reinforcement of the ZA and effectively coupling epithelial morphogenesis and cell polarity [14].

Anatomical context of Cell Polarity

• Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta [15].
• The roles of Cdc42 in stimulating changes in the actin cytoskeleton and in the establishment of cell polarity have been known for some time [16].
• The Côte D'Azure provided a stunning backdrop for a recent conference* on the role of microfilament function and regulation in cell polarity [17].
• Here we review studies of the pathways that allow Ca(2+) entry, the function of Ca(2+) in the regulation of cell polarity and motility and the principles by which Ca(2+)-dependent transcription regulates lymphocyte function [18].
• Despite regaining cell polarity, however, epithelial cells in crb and lgl pathway mutants fail to re-establish normal overall tissue architecture, indicating that the timely acquisition of polarized cell structure is essential for normal tissue organization [19].

Associations of Cell Polarity with chemical compounds

• Cells lacking crumbs or the functionally related gene stardust fail to organize a continuous ZA and to maintain cell polarity [20].
• Thus, GNOM-dependent vesicle trafficking may establish cell polarity, resulting in polar auxin transport [21].
• Addition of the PI3K inhibitor LY294002 results in a rapid loss of cell polarity and the axial distribution of actin, myosin, and PAKa [22].
• The guanine-nucleotide-exchange factor Cdc24 is a critical regulator of cell polarity [23].
• IGF-I stimulation of cholesterol-depleted cells induces projection of multiple pseudopodia over the entire cell periphery, indicating that raft disruption specifically affects the acquisition of cell polarity, but not IGF-I-induced protrusion activity [24].

Gene context of Cell Polarity

• Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled [25].
• The similarity to CRB suggests a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina [26].
• Temperature-sensitive cells with mutations of the CDC24 and CDC42 genes, which are incapable of budding and of generating cell polarity at the restrictive temperature, are also unable to mate [27].
• Therefore, the inability of cdc24 and cdc42 mutants to mate has been presumed to be due to a requirement for generation of cell polarity and related morphogenetic events during conjugation [27].
• We conclude that Cdc42 regulates cell polarity through the spatial regulation of GSK-3beta and Apc [28].

Analytical, diagnostic and therapeutic context of Cell Polarity

• Here we show, using time-lapse confocal microscopy, that the failure of cells lacking Xdsh function to undergo convergent extension results from defects in cell polarity [29].
• Dissection of Arabidopsis ADP-RIBOSYLATION FACTOR 1 function in epidermal cell polarity [30].
• Positional cloning and sequence analysis of the cyk-1 gene reveal that it encodes an FH protein, a newly defined family of proteins that appear to interact with the cytoskeleton during cytokinesis and in the regulation of cell polarity [31].

References