polarity
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Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42. In epithelial tissues, their mutual interplay ensures apico-basal and planar cell polarity. Accordingly, altered functions of these polarity determinants lead to disrupted cell-cell adhesions, cytoskeleton rearrangements and overall loss of epithelial homeostasis. Polarity proteins are further engaged in diverse interactions that promote the establishment of front-rear polarity, and they help cancer cells to adopt different invasion modes. Invading cancer cells can employ either the collective, mesenchymal or amoeboid invasion modes or actively switch between them and gain intermediate phenotypes. Elucidation of the role of polarity proteins during these invasion modes and the associated transitions is a necessary step towards understanding the complex problem of metastasis. In this review we summarize the current knowledge of the role of cell polarity signaling in the plasticity of cancer cell invasiveness.
- Klíčová slova
- AMT, EMT, invasion, plasticity, polarity,
- MeSH
- invazivní růst nádoru patologie MeSH
- lidé MeSH
- nádory patologie MeSH
- polarita buněk fyziologie MeSH
- signální transdukce fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-β/SMAD, and β-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells.
- Klíčová slova
- Cell polarity, Coinfection, EBV, Gastric cancer, Helicobacter pylori,
- MeSH
- Helicobacter pylori * genetika MeSH
- infekce virem Epsteina-Barrové * mikrobiologie patologie MeSH
- infekce vyvolané Helicobacter pylori * mikrobiologie MeSH
- koinfekce * mikrobiologie MeSH
- lidé MeSH
- nádory žaludku * genetika mikrobiologie patologie MeSH
- polarita buněk MeSH
- virové proteiny MeSH
- virus Epsteinův-Barrové genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- virové proteiny MeSH
Cell polarity is a key feature in the development of multicellular organisms. For instance, asymmetrically localized plasma-membrane-integral PIN-FORMED (PIN) proteins direct transcellular fluxes of the phytohormone auxin that govern plant development. Fine-tuned auxin flux is important for root protophloem sieve element differentiation and requires the interacting plasma-membrane-associated BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX) proteins. We observed "donut-like" polar PIN localization in developing sieve elements that depends on complementary, "muffin-like" polar localization of BRX and PAX. Plasma membrane association and polarity of PAX, and indirectly BRX, largely depends on phosphatidylinositol-4,5-bisphosphate. Consistently, mutants in phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) display protophloem differentiation defects similar to brx mutants. The same PIP5Ks are in complex with BRX and display "muffin-like" polar localization. Our data suggest that the BRX-PAX module recruits PIP5Ks to reinforce PAX polarity and thereby the polarity of all three proteins, which is required to maintain a local PIN minimum.
- Klíčová slova
- Arabidopsis, DRP1A, PIP5K1, PIP5K2, endocytosis, phloem, polar auxin transport, polarity, protophloem, root,
- MeSH
- Arabidopsis genetika růst a vývoj metabolismus MeSH
- buněčná diferenciace * MeSH
- buněčná membrána metabolismus MeSH
- fosfatasy genetika metabolismus MeSH
- fosfotransferasy s alkoholovou skupinou jako akceptorem metabolismus MeSH
- kořeny rostlin genetika růst a vývoj metabolismus MeSH
- mutace MeSH
- polarita buněk * MeSH
- proteiny huseníčku genetika metabolismus MeSH
- regulace genové exprese u rostlin * MeSH
- transkripční faktory paired box genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1-phosphatidylinositol-4-phosphate 5-kinase MeSH Prohlížeč
- BREVIS RADIX protein, Arabidopsis MeSH Prohlížeč
- CVP2 protein, Arabidopsis MeSH Prohlížeč
- fosfatasy MeSH
- fosfotransferasy s alkoholovou skupinou jako akceptorem MeSH
- proteiny huseníčku MeSH
- transkripční faktory paired box MeSH
Actomyosin contractility represents an ancient feature of eukaryotic cells participating in many developmental and homeostasis events, including tissue morphogenesis, muscle contraction and cell migration, with dysregulation implicated in various pathological conditions, such as cancer. At the molecular level, actomyosin comprises actin bundles and myosin motor proteins that are sensitive to posttranslational modifications like phosphorylation. While the molecular components of actomyosin are well understood, the coordination of contractility by extracellular and intracellular signals, particularly from cellular signalling pathways, remains incompletely elucidated. This study focuses on WNT/planar cell polarity (PCP) signalling, previously associated with actomyosin contractility during vertebrate neurulation. Our investigation reveals that the main cytoplasmic PCP proteins, Prickle and Dishevelled, interact with key actomyosin components such as myosin light chain 9 (MLC9), leading to its phosphorylation and localized activation. Using proteomics and microscopy approaches, we demonstrate that both PCP proteins actively control actomyosin contractility through Rap1 small GTPases in relevant in vitro and in vivo models. These findings unveil a novel mechanism of how PCP signalling regulates actomyosin contractility through MLC9 and Rap1 that is relevant to vertebrate neurulation.
- Klíčová slova
- MDCK cells, Xenopus embryos, actomyosin contractility, neurulation, planar cell polarity, vertebrates,
- MeSH
- aktomyosin * metabolismus MeSH
- fosforylace MeSH
- lehké řetězce myosinu metabolismus MeSH
- lidé MeSH
- myši MeSH
- neurulace * MeSH
- obratlovci metabolismus MeSH
- polarita buněk * MeSH
- protein dishevelled metabolismus genetika MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aktomyosin * MeSH
- lehké řetězce myosinu MeSH
- protein dishevelled MeSH
During the first cell-fate decision of mouse preimplantation embryo development, a population of outer-residing polar cells is segregated from a second population of inner apolar cells to form two distinct cell lineages: the trophectoderm and the inner cell mass (ICM), respectively. Historically, two models have been proposed to explain how the initial differences between these two cell populations originate and ultimately define them as the two stated early blastocyst stage cell lineages. The 'positional' model proposes that cells acquire distinct fates based on differences in their relative position within the developing embryo, while the 'polarity' model proposes that the differences driving the lineage segregation arise as a consequence of the differential inheritance of factors, which exhibit polarized subcellular localizations, upon asymmetric cell divisions. Although these two models have traditionally been considered separately, a growing body of evidence, collected over recent years, suggests the existence of a large degree of compatibility. Accordingly, the main aim of this review is to summarize the major historical and more contemporarily identified events that define the first cell-fate decision and to place them in the context of both the originally proposed positional and polarity models, thus highlighting their functional complementarity in describing distinct aspects of the developmental programme underpinning the first cell-fate decision in mouse embryogenesis.
- Klíčová slova
- cell positioning and polarity, cell-fate, preimplantation mouse embryo,
- MeSH
- biologické modely * MeSH
- buněčný rodokmen MeSH
- embryo savčí cytologie fyziologie MeSH
- embryonální vývoj fyziologie MeSH
- polarita buněk * MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Cell polarity is crucial for the coordinated development of all multicellular organisms. In plants, this is exemplified by the PIN-FORMED (PIN) efflux carriers of the phytohormone auxin: The polar subcellular localization of the PINs is instructive to the directional intercellular auxin transport, and thus to a plethora of auxin-regulated growth and developmental processes. Despite its importance, the regulation of PIN polar subcellular localization remains poorly understood. Here, we have employed advanced live-cell imaging techniques to study the roles of microtubules and actin microfilaments in the establishment of apical polar localization of PIN2 in the epidermis of the Arabidopsis root meristem. We report that apical PIN2 polarity requires neither intact actin microfilaments nor microtubules, suggesting that the primary spatial cue for polar PIN distribution is likely independent of cytoskeleton-guided endomembrane trafficking.
- Klíčová slova
- PIN auxin efflux carriers, actin, cell polarity, cytoskeleton, live-cell imaging, microtubules, polarity establishment,
- MeSH
- Arabidopsis cytologie metabolismus MeSH
- cytoskelet metabolismus MeSH
- intracelulární prostor metabolismus MeSH
- proteiny huseníčku metabolismus MeSH
- transport proteinů MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- PIN2 protein, Arabidopsis MeSH Prohlížeč
- proteiny huseníčku MeSH
Cell polarity, the asymmetric organization of cellular components along one or multiple axes, is present in most cells. From budding yeast cell polarization induced by pheromone signaling, oocyte polarization at fertilization to polarized epithelia and neuronal cells in multicellular organisms, similar mechanisms are used to determine cell polarity. Crucial role in this process is played by signaling lipid molecules, small Rho family GTPases and Par proteins. All these signaling circuits finally govern the cytoskeleton, which is responsible for oriented cell migration, cell shape changes, and polarized membrane and organelle trafficking. Thus, typically in the process of cell polarization, most cellular constituents become polarized, including plasma membrane lipid composition, ion concentrations, membrane receptors, and proteins in general, mRNA, vesicle trafficking, or intracellular organelles. This review gives a brief overview how these systems talk to each other both during initial symmetry breaking and within the signaling feedback loop mechanisms used to preserve the polarized state.
- Klíčová slova
- Cell polarization, Cell signaling, Chemotaxis, Neurite initiation, Par proteins, Rho GTPases,
- MeSH
- membránové proteiny metabolismus MeSH
- mikrofilamenta metabolismus MeSH
- mikrotubuly metabolismus MeSH
- nádorové proteiny metabolismus MeSH
- neutrofily metabolismus MeSH
- pohyb buněk fyziologie MeSH
- polarita buněk fyziologie MeSH
- Rho proteiny vázající GTP metabolismus MeSH
- signální transdukce fyziologie MeSH
- tvar buňky fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- JTB protein, human MeSH Prohlížeč
- membránové proteiny MeSH
- nádorové proteiny MeSH
- Rho proteiny vázající GTP MeSH
Polar subcellular localization of the PIN exporters of the phytohormone auxin is a key determinant of directional, intercellular auxin transport and thus a central topic of both plant cell and developmental biology. Arabidopsis mutants lacking PID, a kinase that phosphorylates PINs, or the MAB4/MEL proteins of unknown molecular function display PIN polarity defects and phenocopy pin mutants, but mechanistic insights into how these factors convey PIN polarity are missing. Here, by combining protein biochemistry with quantitative live-cell imaging, we demonstrate that PINs, MAB4/MELs, and AGC kinases interact in the same complex at the plasma membrane. MAB4/MELs are recruited to the plasma membrane by the PINs and in concert with the AGC kinases maintain PIN polarity through limiting lateral diffusion-based escape of PINs from the polar domain. The PIN-MAB4/MEL-PID protein complex has self-reinforcing properties thanks to positive feedback between AGC kinase-mediated PIN phosphorylation and MAB4/MEL recruitment. We thus uncover the molecular mechanism by which AGC kinases and MAB4/MEL proteins regulate PIN localization and plant development.
- Klíčová slova
- Arabidopsis, cell polarity, lateral diffusion, plant development, polar auxin transport, positive feedback, protein phosphorylation,
- MeSH
- Arabidopsis * genetika metabolismus MeSH
- biologický transport MeSH
- kořeny rostlin metabolismus MeSH
- kyseliny indoloctové MeSH
- membránové transportní proteiny genetika MeSH
- polarita buněk MeSH
- proteiny huseníčku * genetika metabolismus MeSH
- regulace genové exprese u rostlin MeSH
- rostlinné buňky metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kyseliny indoloctové MeSH
- membránové transportní proteiny MeSH
- proteiny huseníčku * MeSH
Brassinosteroid hormones are positive regulators of plant organ growth, yet their function in proliferating tissues remains unclear. Here, through integrating single-cell RNA sequencing with long-term live-cell imaging of the Arabidopsis root, we reveal that brassinosteroid activity fluctuates throughout the cell cycle, decreasing during mitotic divisions and increasing during the G1 phase. The post-mitotic recovery of brassinosteroid activity is driven by the intrinsic polarity of the mother cell, resulting in one daughter cell with enhanced brassinosteroid signaling, while the other supports brassinosteroid biosynthesis. The coexistence of these distinct daughter cell states during the G1 phase circumvents a negative feedback loop to facilitate brassinosteroid production while signaling increases. Our findings uncover polarity-guided, uneven mitotic divisions in the meristem, which control brassinosteroid hormone activity to ensure optimal root growth.
- Klíčová slova
- brassinosteroids, cell cycle, cell division, cell polarity, live-cell imaging, root meristem, single-cell RNA sequencing,
- MeSH
- Arabidopsis * metabolismus cytologie růst a vývoj MeSH
- brassinosteroidy * metabolismus MeSH
- kořeny rostlin * cytologie metabolismus růst a vývoj MeSH
- meristém metabolismus cytologie MeSH
- mitóza * MeSH
- polarita buněk * MeSH
- proliferace buněk MeSH
- proteiny huseníčku metabolismus genetika MeSH
- regulace genové exprese u rostlin MeSH
- regulátory růstu rostlin metabolismus MeSH
- signální transdukce MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- brassinosteroidy * MeSH
- proteiny huseníčku MeSH
- regulátory růstu rostlin MeSH