Transcriptional Control of Apical-Basal Polarity Regulators

Abstract

Cell polarity is essential for many functions of cells and tissues including the initial establishment and subsequent maintenance of epithelial tissues, asymmetric cell division, and morphogenetic movements. Cell polarity along the apical-basal axis is controlled by three protein complexes that interact with and co-regulate each other: The Par-, Crumbs-, and Scrib-complexes. The localization and activity of the components of these complexes is predominantly controlled by protein-protein interactions and protein phosphorylation status. Increasing evidence accumulates that, besides the regulation at the protein level, the precise expression control of polarity determinants contributes substantially to cell polarity regulation. Here we review how gene expression regulation influences processes that depend on the induction, maintenance, or abolishment of cell polarity with a special focus on epithelial to mesenchymal transition and asymmetric stem cell division. We conclude that gene expression control is an important and often neglected mechanism in the control of cell polarity.

A microwell platform for high-throughput longitudinal phenotyping and selective retrieval of organoids

“…Consistent with this potential role, SP family TFs were more highly bound to upstream promoter regions of several genes such as PPP2R1B and LLGL1 involved in establishing epithelial apical-basal polarity (Fig. 5H) (59,62,63). The RNA-seq data corroborated these findings, as multiple upregulated genes with known SP family target sites were differentially expressed in normal versus abnormal polarity organoids (Fig.…”

“…At a molecular level, transcription factor (TF) footprinting analysis of the ATAC-seq data indicated that organoids with abnormal polarity had increased accessibility in chromosomal regions bound by the SP family TFs (Fig. 5G), which are involved in maintaining epithelial cell polarity (58,59) and are dysregulated in a variety of cancer types (60,61). Consistent with this potential role, SP family TFs were more highly bound to upstream promoter regions of several genes such as PPP2R1B and LLGL1 involved in establishing epithelial apical-basal polarity (Fig.…”

The Versatile Role of Uromodulin in Renal Homeostasis and Its Relevance in Chronic Kidney Disease

“…Furthermore, NKCC2 phosphorylation was significantly decreased in Umod -/- mice ( 38 ). Because apical expression and phosphorylation are essential for the membrane protein function ( 39 ), the downregulation of apical expression and phosphorylation of NKCC2 in Umod -/- mice indicates defective transporter activation. The loss of function of NKCC2 generates a phenotype similar to Bartter syndrome, a salt-losing tubulopathy.…”

Diamond controls epithelial polarity through the dynactin‐dynein complex

“…Metazoan epithelial cells, highly polarized along their apico‐basal (A/B) axis, connect with each other via a variety of inter‐cellular junctions and the polarization is critical for the structure and functions of the epithelial tissues they comprise 1–10 . Disruption of epithelial polarity is often associated with tumorigenesis and metastasis 11,12 . The epithelial plasma membranes are divided into distinct domains along their A/B axis.…”