Polarity proteins

Cell polarity is crucial for the development of multicellular organisms, and aberrant cell polarization contributes to various diseases. Seminal studies in invertebrates identified proteins that regulate various polarization processes including asymmetric cell division and epithelial cell polarization. Polarity proteins may react to extrinsic polarity cues such as growth factor gradients, or intrinsic cues such as the microtubule cytoskeleton. By assembling multiprotein complexes, they induce downstream signaling to establish cellular asymmetry (Dias Gomes & Iden, 2021). Of the three polarity protein complexes described so far – Par3, Crumbs and Scribble – the Par3 complex appears to have the broadest function. Furthermore, cross-talk between polarity proteins and Rho GTPase signaling components controls formation of cell-cell contacts and apico-basal polarity in epithelial cells (Iden & Collard 2008). Through interaction with transmembrane or cytoplasmic proteins, the Par3 polarity complex acts at various subcellular sites to regulate cellular asymmetry. During epithelial cell-cell contact formation, the TJ protein Junctional Adhesion Molecule-A (JAM-A) serves to recruit Par3 to intercellular junctions. For decades, loss of apico-basal polarity has been considered a prerequisite for tumor formation and progression (Mescher & Iden 2015), though functional evidence is still limited.