PARD3

PARD3, or partitioning defective 3 homolog, is a human gene encoding a polarity-associated scaffold protein that participates in the establishment and maintenance of cell polarity.

In mammalian cells, the PARD3-encoded protein localizes to tight junctions and forms part of the PAR polarity complex with PARD6 and aPKC. This complex coordinates the segregation of apical and basolateral domains and promotes tight junction maturation and epithelial barrier function.

Molecularly, PARD3 proteins contain three PDZ domains that mediate interactions with multiple polarity regulators and signaling proteins, enabling them to recruit and organize components at the cell cortex. Through these interactions, Par-3 controls cytoskeletal organization and vesicle trafficking required for polarity.

Biological significance: PARD3 plays a role in epithelial morphogenesis, asymmetric cell division, and ciliogenesis in some tissues. Loss or mislocalization of PARD3 can disrupt polarity, contribute to lumen formation defects, and influence cell migration.

Clinical relevance: Alterations of PARD3, including mutations and reduced expression, have been reported in several cancers. In many contexts, PARD3 functions as a tumor suppressor by preserving epithelial polarity; its loss may promote epithelial-to-mesenchymal transition and tumor progression.