Research ArticleCell Biology

Structural basis for the interaction between the cell polarity proteins Par3 and Par6

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Science Signaling  13 Feb 2018:
Vol. 11, Issue 517, eaam9899
DOI: 10.1126/scisignal.aam9899

Building a polarity scaffold

Cell types often exhibit asymmetric distributions of proteins, lipids, and organelles that are linked to specialized functions, and loss of polarization precedes pathological conditions such as cancer. The cell polarity proteins Par3 and Par6 and the kinase aPKC are critical for generating asymmetry in cells. Par3 and Par6 contain multiple PDZ domains, which bind to short motifs to enable protein-protein interactions. Using biochemical analyses, cultured cells, and fly embryos, Renschler et al. identified a PDZ domain–binding motif in Par6 that bound to two of the three PDZ domains in Par3. These results suggest that one Par3 protein could bind to two Par6 proteins, which could serve as the basis for polarity-generating protein scaffolds in cells.


Polarity is a fundamental property of most cell types. The Par protein complex is a major driving force in generating asymmetrically localized protein networks and consists of atypical protein kinase C (aPKC), Par3, and Par6. Dysfunction of this complex causes developmental abnormalities and diseases such as cancer. We identified a PDZ domain–binding motif in Par6 that was essential for its interaction with Par3 in vitro and for Par3-mediated membrane localization of Par6 in cultured cells. In fly embryos, we observed that the PDZ domain–binding motif was functionally redundant with the PDZ domain in targeting Par6 to the cortex of epithelial cells. Our structural analyses by x-ray crystallography and NMR spectroscopy showed that both the PDZ1 and PDZ3 domains but not the PDZ2 domain in Par3 engaged in a canonical interaction with the PDZ domain–binding motif in Par6. Par3 thus has the potential to recruit two Par6 proteins simultaneously, which may facilitate the assembly of polarity protein networks through multivalent PDZ domain interactions.

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