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Cell polarity  Cell polarity, asymmetric distribution of cellular components

Cell polarity is a conserved evolutionary process found in most organisms, and is essential for many functions of cells and tissues including the initial establishment and subsequent maintenance of epithelial tissues, asymmetric cell division, cell motility, cell differentiation, morphogenetic movements, and tissue repair.

It is characterized by the asymmetric distribution of cellular proteins, membranes, organelles and processes within the cell. The regulation of this process is very important for cell function, and cells use various mechanisms to ensure appropriate abundance and activity of polarity determinants (1,2,,3,4).

signaling pathway what are the components of polarity process ?

Three evolutionary conserved polarity complexes govern cellular polarity: Scribble (Scrib), the apically localized Partitioning defective (Par) et Crumbs (Crb).
  • Par complex exerts a major function in regulating the phosphorylation state of polarity determinants, including components of the Par complex itself and of additional targets whose localization and/or activity is influenced by phosphorylation.
  • Scrib complex consists of the scaffold proteins Scribble (Scrib), Lethal giant larvae (Lgl), and Discs large (Dlg), all of which are composed of multiple protein-protein interaction domains.
  • Crb complex exerts its function via the regulation and facilitation of protein-protein interactions.
  • cell polarity (epithelial cells)

    Apico-basal polarity (epithelial cells). In mammalian epithelial cells, development of an apico-basal polarity
    allows the organization of two well defined domains separated by tight junctions.

    cell polarity

    In slow migrating cells such as fibroblasts, astrocytes and epithelial cells, a polarized organization of intracellular molecules
    and structures allow the formation and maintenance of a leading edge with membrane extensions and the retraction
    of the rear of the cell. These regulations allow a sustained orientation of migration into the desired direction.

    Summary of the main polarity-defining molecules described in this review and involved in various polarity model systems (5)

    The members of these complexes function as protein magnets through their ability to bind or repel polarising organelles, cytoplasmic structures, cytoskeletal components, and cell fate determinant proteins (2,4). This complexes can facilitate either stable polarized states leading to specialized functional areas in tissues and organs, or adaptive polarization occurring, for example, during wound healing or immune cell responses (1).

    The localization and activity of polarity proteins is strongly regulated through kinases and phosphatases (2).

    Polarity of cell is crucial during embryogenesis, and for maintenance of tissue architecture and homeostasis, wound healing, immune responses ...
    This active process is triggered and maintained by extracellular signals transmitted by neighboring cells and/or the surrounding microenvironment. Even stably polarized tissues, such as the epithelium, must maintain polarization signals to control the transition between mesenchymal and epithelial states and vice versa.
    Extracellular signals for the cellular polarity process are translated into a tightly regulated cascade of events that, if altered, can lead to disease states, including developmental abnormalities or tumorigenesis (1).

    Cell polarity  Cell polarity and diseases

    The polarity of cell is closely related to cell proliferation and growth. Accordingly, many cellular polarity determinants have suppressive or pro-oncogenic properties and have been reported to be poorly regulated in a variety of different tumors, particularly those of epithelial origin (2,4).
    (1)  Mastrogiovanni M, et al. Cell polarity regulators, multifunctional organizers of lymphocyte activation and function. Biomed J. (2022);45(2):299-309.
    (2)   Rust K, Wodarz A. Transcriptional Control of Apical-Basal Polarity Regulators. Int J Mol Sci. (2021);22(22):12340. (2017).
    (3)  Guzmán-Herrera A, Mao Y. Polarity during tissue repair, a multiscale problem. Curr Opin Cell Biol. (2020); 62: 31–36.
    (4)    Atashrazm F, Ellis S. The polarity protein PARD3 and cancer. Oncogene. (2021);40(25):4245-4262.
    (5)  Jossin Y. Molecular mechanisms of cell polarity in a range of model systems and in migrating neurons. Mol Cell Neurosci. (2020);106:103503.
     
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