PAR3PAR6aPKC

Par3-Par6-aPKC is a conserved protein complex that governs cell polarity in metazoans. The core components are Par3 (Partitioning-defective 3), Par6 (PARD6A/B/G), and an atypical protein kinase C (aPKC). In mammals, the aPKC members are PKC zeta and PKC iota (PRKCZ and PRKCI). The complex acts as a polarity scaffold and signaling hub that coordinates the asymmetric distribution of membrane proteins, cytoskeletal elements, and vesicle trafficking to establish and maintain apical-basal polarity in epithelial cells and polarized processes in neurons.

Par3 serves as a scaffold with PDZ domains that bind junctional and polarity proteins. Par6 contains a PB1 domain that mediates heterodimerization with aPKC and interactions with small GTPases such as Cdc42/Rac. aPKC is a serine/threonine kinase whose activity and localization are regulated by complex formation and by small GTPases. The complex is typically localized to the apical region of epithelial cells at tight junctions and interacts with other polarity modules, including Crumbs and Scribble, to coordinate polarity cues.

Functionally, the Par3-Par6-aPKC complex establishes the apical domain, promotes lumen formation, and organizes cytoskeletal dynamics and vesicle trafficking. It also participates in asymmetric cell division in certain progenitor cells. Regulation occurs through phosphorylation events—often involving aPKC-mediated phosphorylation of Par3 and Par6—and through interactions with Cdc42-GTP and other polarity regulators.

Disruption of the Par complex can lead to loss of epithelial barrier function and is associated with developmental defects and tumorigenesis. The complex is preserved across species and forms part of a broader polarity network that includes additional complexes such as Crumbs and Scribble.