Signaling via the Rho GTPases provides crucial regulation of numerous cell polarization events, including apicobasal (AB) polarity, polarized cell migration, polarized cell division and neuronal polarity. Here we review the relationships between the Rho family GTPases and epithelial AB polarization events, focusing on the 3 best-characterized members: Rho, Rac and Cdc42. We discuss a multitude of processes that are important for AB polarization, including lumen formation, apical membrane specification, cell-cell junction assembly and maintenance, as well as tissue polarity. Our discussions aim to highlight the immensely complex regulatory mechanisms that encompass Rho GTPase signaling during AB polarization. More specifically, in this review we discuss several emerging common themes, that include: 1) the need for Rho GTPase activities to be carefully balanced in both a spatial and temporal manner through a multitude of mechanisms; 2) the existence of signaling feedback loops and crosstalk to create robust cellular responses; and 3) the frequent multifunctionality that exists among AB polarity regulators. Regarding this latter theme, we provide further discussion of the potential plasticity of the cell polarity machinery and as a result the possible implications for human disease.
Keywords: AB, Apicobasal; AJ, Adherens junction; Amot, Angiomotin; Arp2/3, Actin-related protein-2/3; Baz, Bazooka; C. elegans, Caenorhabditis elegans; CA, Constitutively-active; CD2AP, CD2-associated protein; Caco2, Human colon carcinoma; Cdc42; Cora, Coracle; Crb, Crumbs; DN, Dominant-negative; Dia1, Diaphanous-related formin 1; Dlg, Discs large; Drosophila, Drosophila melanogaster; Dys-β, Dystrobrevin-β; ECM, Extracellular matrix; Ect2, Epithelial cell transforming sequence 2 oncogene; Eya1, Eyes absent 1; F-actin, Filamentous actin; FRET, Fluorescence resonance energy transfer; GAP, GTPase-activating protein; GDI, Guanine nucleotide dissociation inhibitor; GEF, Guanine nucleotide exchange factor; GTPases; JACOP, Junction-associated coiled-coiled protein; JAM, Junctional adhesion molecule; LKB1, Liver kinase B1; Lgl, Lethal giant larvae; MDCK, Madin-Darby canine kidney; MTOC, Microtubule-organizing center; NrxIV, Neurexin IV; Pals1, Protein associated with Lin-7 1; Par, Partitioning-defective; Patj, Pals1-associated TJ protein; ROCK, Rho-associated kinase; Rac; Rho; Rich1, RhoGAP interacting with CIP4 homologues; S. cerevisiae, Saccharomyces cerevisiae; S. pombe, Schizosaccharomyces pombe; SH3BP1, SH3-domain binding protein 1; Scrib, Scribble; Std, Stardust; TEM4, Tumor endothelial marker 4; TJ, Tight junction; Tiam1, T-cell lymphoma invasion and metastasis-inducing protein 1; WASp, Wiskott-aldrich syndrome protein; Yrt, Yurt; ZA, zonula adherens; ZO, Zonula occludens; aPKC, Atypical Protein Kinase C; apicobasal; epithelia; junction; par; polarity; α-cat, Alpha-catenin; β-cat, Beta-Catenin; β2-syn, Beta-2-syntrophin.