Protein complexes that control renal epithelial polarity

Abstract

Establishment of epithelial apicobasal polarity is crucial for proper kidney development and function. In recent years, there have been important advances in our understanding of the factors that mediate the initiation of apicobasal polarization. Key among these are the polarity complexes that are evolutionarily conserved from simple organisms to humans. Three of these complexes are discussed in this review: the Crumbs complex, the Par complex, and the Scribble complex. The apical Crumbs complex consists of three proteins, Crumbs, PALS1, and PATJ, whereas the apical Par complex consists of Par-3, Par-6, and atypical protein kinase C. The lateral Scribble complex consists of Scribble, discs large, and lethal giant larvae. These complexes modulate kinase and small G protein activity such that the apical and basolateral complexes signal antagonistically, leading to the segregation of the apical and basolateral membranes. The polarity complexes also serve as scaffolds to direct and retain proteins at the apical membrane, the basolateral membrane, or the intervening tight junction. There is plasticity in apicobasal polarity, and this is best seen in the processes of epithelial-to-mesenchymal transition and the converse mesenchymal-to-epithelial transition. These transitions are important in kidney disease as well as kidney development, and modulation of the polarity complexes are critical for these transitions.

Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities

“…We finally compared the distribution of ABP components in Nectin-3 +/-and Nectin-3 -/-auditory epithelia. Three major ABP complexes, namely, the apical Crumbs complex consisting of Crumbs3 (Crb3), Pals1 (Mpp5 -Mouse Genome Informatics) and Pals1-associated tight junction protein (Patj), the Par complex consisting of Par-3, Par-6 (Pard6 -Mouse Genome Informatics) and atypical protein kinase C (aPKC), and the lateral Scribble complex consisting of Scribble, discs large (Dlg1) and Lgl, are essential for epithelial ABP formation (Pieczynski and Margolis, 2011). In the surface view of the Nectin-3 +/-auditory epithelium, the immunofluorescence signal for Pals1 was concentrated at the phalloidin-negative apical surface of HCs, which was polarised towards the lateral side (Fig.…”

Centrosome positioning in vertebrate development

“…The Par complex (see Box 1) is a set of evolutionarily conserved intrinsic polarity proteins, consisting of Par3, Par6 and atypical protein kinase C (aPKC), which are asymmetrically distributed at the cell cortex and have important functions in the determination of cell polarity and the orientation of the mitotic spindle (Pieczynski and Margolis, 2011). The Par complex is a main determinant of polarity.…”

“…The Par complex, consisting of Par3, Par6 and atypical protein kinase C (aPKC), localizes to the apical cortex of epithelial cells in vertebrates, the anterior cortex in the C. elegans zygote and the apical cortex in Drosophila neuroblasts (Pieczynski and Margolis, 2011). Par3 contains multiple PDZ domains and provides anchorage to assemble the Par complex at the apical-lateral border by binding Par6 and recruiting Par6-associated proteins.…”

Apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state

“…Polarity complexes include evolutionarily conserved apical complex proteins, such as the Crb complex (comprising Crbs, Pals1, Patj), the Par complex (Par3, Par6, aPKC) and basal complex proteins, such as the Scribble complex (Scribbles, Lgl, Dlg) (Assémat et al, 2008;Pieczynski and Margolis, 2011;Tepass, 2012). Previous studies have demonstrated that apical complex proteins are necessary for self-renewal of neural progenitor cells (Bultje et al, 2009;Costa et al, 2008;Kim et al, 2010), neuronal migration (Famulski et al, 2010;Solecki et al, 2006), axon determination (Chen et al, 2013;Shi et al, 2003), dendrite development (Tanabe et al, 2010), tissue polarity and neuron survival (Kim et al, 2010).…”