PARaPKC

PARaPKC refers to a conserved polarity module in metazoan cells consisting of the adaptor protein PAR-3, the scaffold protein PAR-6, and an atypical protein kinase C (aPKC). In most animals, this complex localizes to the apical cortex of epithelial cells and to the prospective polarity domain in dividing cells, where it coordinates the establishment and maintenance of cell polarity.

PAR-6 binds to active Cdc42 and recruits aPKC, whose kinase activity is regulated by PAR-6 and PAR-3. PAR-3 acts as a scaffolding platform that anchors the complex to the cortex and orchestrates the assembly of polarity proteins. Activation of aPKC leads to phosphorylation of downstream substrates such as PAR-3 itself, and other polarity regulators like Lgl and Numb, promoting apical identity and restricting basolateral determinants.

Functionally, PARaPKC contributes to epithelial tight and adherens junction formation, apical-basal polarity, vesicle trafficking, and cytoskeletal organization. It also plays a pivotal role in embryonic development and stem cell divisions, notably in Drosophila neuroblasts and the C. elegans zygote, where it helps regulate asymmetric cell division by controlling the localization of cell fate determinants and spindle orientation.

Regulation and interactions involve antagonism with the Scribble polarity module, which defines basolateral identity. PAR-1 kinase can phosphorylate PAR-3 to promote its exclusion from the basal domain, while Crumbs and other apical regulators cooperate with PARaPKC to establish the apical domain.

Conservation and significance: the PARaPKC module is highly conserved among metazoans. Polarity defects involving this complex can disrupt tissue organization and have been linked to developmental abnormalities and, in some contexts, cancer progression, underscoring its central role in development and cell biology.