Complex Polarity: Building Multicellular Tissues Through Apical Membrane Traffic

Abstract

The formation of distinct subdomains of the cell surface is crucial for multicellular organism development. The most striking example of this is apical-basal polarization. What is much less appreciated is that underpinning an asymmetric cell surface is an equally dramatic intracellular endosome rearrangement. Here, we review the interplay between classical cell polarity proteins and membrane trafficking pathways, and discuss how this marriage gives rise to cell polarization. We focus on those mechanisms that regulate apical polarization, as this is providing a number of insights into how membrane traffic and polarity are regulated at the tissue level.

Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition

“…The RhoA-ROCK1 signalling pathway is a major regulator of polarity orientation [3, 4, 6, 7], and our current and previous results indicate that it must be under strict spatiotemporal control to allow for the correct orientation of apical-basal polarization. Inhibition of RhoA-ROCK1 signalling appears to be a common requirement for robust polarization in 3D contexts, for a growing list of cell types, including MDCK cysts [6, 7, 18], Calu-3 as indicated here, and explants of primary human intestinal cells [14].…”

“…Lumen formation in diverse contexts requires a complex interplay between basolateral polarity complexes (Scribble, Discs Large, Lethal Giant Larvae) and the apical complexes (Crumbs/Pals1/PatJ, and Par3-aPKC-Par6-Cdc42) [4]. Mutual antagonism between basolateral and apical complexes ensure that asymmetry between different subdomains of the cell surface can occur [2].…”

“…For instance, in an apical-basal polarized epithelial cell, both apical and basolateral polarity complexes interact with spindle-orientation machinery so that cell divisions occur in the plane of the epithelium, ensuring that cells do not divide into the lumen. The apical component, aPKC, masterminds this process [4]. Interestingly, aPKC and ROCK1/2 exist in antagonism for phosphorylation of Par3 [4].…”

“…The apical component, aPKC, masterminds this process [4]. Interestingly, aPKC and ROCK1/2 exist in antagonism for phosphorylation of Par3 [4]. APKC can phosphorylate Par3, which acts to uncouple Par3 from the Cdc42-aPKC-Par6 complex.…”

“…While the mechanisms of how apical-basal polarity is formed have been extensively investigated [1, 2] how such polarity is oriented has until recently been neglected [3, 4]. Traditional culture methods for epithelial cells involves growth of cells to become apical-basal polarized monolayers on rigid substrata such as glass, plastic, or semi-permeable membrane filters.…”