Abstract
Cell polarity is a key feature of many eukaryotic cells, including neurons, epithelia, endothelia and asymmetrically dividing stem cells. Apart from the specific localization of proteins to distinct domains of the plasma membrane, most of these cells exhibit an asymmetric distribution of phospholipids within the plasma membrane too. Notably, research over the last years has revealed that many known conserved regulators of apical-basal polarity in epithelial cells are capable of binding to phospholipids, which in turn regulate the localization and to some extent the function of these proteins. Conversely, phospholipid-modifying enzymes are recruited and controlled by polarity regulators, demonstrating an elaborated balance between asymmetrically localized proteins and phospholipids, which are enriched in certain (micro)domains of the plasma membrane. In this review, we will focus on our current understanding of apical-basal polarity and the implication of phospholipids within the plasma membrane during the cell polarization of epithelia and migrating cells.
Highlights
One of the fundamental prerequisites for the function of epithelial cells is the polarization along their apical-basal axis
A possible hint comes from migrating epithelial cells, in which phosphatidic acid (PA) is enriched at the rear rather than at the leading edge (FerrazNogueira et al, 2014), which would be in contradiction to the proposed role of LKB1 at the leading edge of migrating cancer cells (Zhang S. et al, 2008)
Emerging evidences suggest a critical role of phospholipids in regulating polarity proteins’ localization and function in polarized epithelial and migrating cells and vice versa: Polarity proteins regulate the accumulation of distinct phospholipids in different membrane compartments by localizing the respective enzymes, e.g., PI3K accumulation at focal adhesions or PTEN targeting at apical junctions
Summary
One of the fundamental prerequisites for the function of epithelial cells is the polarization along their apical-basal axis. This apical-basal polarity is established and regulated by a set of highly conserved polarity determinants (Table 1), which act in antagonizing fashions in order to keep the balance between the apical and the basolateral plasma membrane domain. Most key determinants of this epithelial apical-basal polarity regulate anterior-posterior polarity in the zygote of Caenorhabditis elegans and the oocyte of Drosophila as well as front-rear polarity in migrating cells (for review see St Johnston and Ahringer, 2010; Tepass, 2012; Rodriguez-Boulan and Macara, 2014; Campanale et al, 2017). PAR-6 is regulated by the small GTPase Cdc, which dynamically associates with the PAR-complex too
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