Par6aPKC

Par6aPKC refers to the protein complex formed by the scaffolding protein Par-6 and the atypical protein kinase C (aPKC), a highly conserved module that regulates cell polarity in animals. In many organisms, Par-6 teams with aPKC and Par-3 to form the core Par complex, which localizes to the apical cortex of epithelial cells and to the polarity axis of asymmetric cell divisions.

The Par6aPKC complex functions to establish, maintain, and propagate cellular polarity. It concentrates at specific membrane domains to coordinate the formation of tight junctions in epithelia and to orient the apical domain during development. In neural progenitors and other dividing cells, the complex helps orient the mitotic spindle and segregate polarity determinants, guiding asymmetric division and fate specification.

Mechanistically, Par-6 acts as a scaffold that brings together aPKC and Par-3, enabling localized activation of aPKC. Activated aPKC phosphorylates downstream substrates, such as polarity determinants, to restrict them to non-apical regions. This phosphorylation reinforces apical domains and suppresses inappropriate localization of basolateral factors. The assembly and activity of the Par6aPKC complex are modulated by Rho family GTPases, phosphoinositide signaling, and interactions with Par-3 and other polarity regulators.

Evolution and isoforms: The Par-6 family is evolutionarily conserved across metazoa. Mammals express multiple Par-6 isoforms (for example Par-6α, Par-6β, Par-6γ) that can partner with aPKC variants to fulfill tissue- and context-specific roles. In invertebrates such as Drosophila, the Par complex functions similarly with species-specific components.

Clinical relevance: Disruption of polarity pathways involving Par-6 and aPKC is linked to developmental disorders and contributes to cancer progression by promoting loss of epithelial organization and controlled growth.