Figure 3.

Epithelial and endothelial apicobasal polarity. (a) Molecular mechanisms of epithelial apicobasal polarity. For details see text. The straight arrow indicates activation, straight dashed arrows indicate phosphorylation, and curved arrows indicate enzymatic reactions. (b) Molecular mechanisms that establish endothelial apicobasal polarity during vascular lumen formation. Only molecules for which functional roles have been demonstrated in vivo are depicted. For further details see text. Similar to epithelial cells, β1 integrin-matrix interactions provide an initial cue to establish endothelial apicobasal polarity.⁶⁰ β1 integrin is required for proper PAR-3 expression levels and for the correct localization of VE-cadherin at lateral cell-cell contacts.⁶⁰ VE-cadherin, which can bind directly to PAR-3,²⁰² forms a complex with CCM1.⁹ CCM1 stabilizes VE-cadherin at adherens junctions to further establish and maintain endothelial apicobasal polarity.^9,203 Rasip1 and its binding partner Arhgap29 suppress the activity of the small GTPase RHOA to promote integrin-mediated adhesion, and to regulate the correct localization of PAR-3, as well as of intercellular junctions.²⁰⁴ In contrast to epithelial cells, the organization of tight and adherens junctions in endothelial cells is less clearly defined, with tight and adherens junctions frequently being intermingled. CCM1: cerebral cavernous malformations 1; Rasip1: Ras interacting protein 1.