The Par3 polarity protein is an exocyst receptor essential for mammary cell survival.

Ahmed SM, Macara IG
Nat Commun. 2017 8: 14867

PMID: 28358000 · PMCID: PMC5379108 · DOI:10.1038/ncomms14867

The exocyst is an essential component of the secretory pathway required for delivery of basolateral proteins to the plasma membranes of epithelial cells. Delivery occurs adjacent to tight junctions (TJ), suggesting that it recognizes a receptor at this location. However, no such receptor has been identified. The Par3 polarity protein associates with TJs but has no known function in membrane traffic. We now show that, unexpectedly, Par3 is essential for mammary cell survival. Par3 silencing causes apoptosis, triggered by phosphoinositide trisphosphate depletion and decreased Akt phosphorylation, resulting from failure of the exocyst to deliver basolateral proteins to the cortex. A small region of PAR3 binds directly to Exo70 and is sufficient for exocyst docking, membrane-protein delivery and cell survival. PAR3 lacking this domain can associate with the cortex but cannot support exocyst function. We conclude that Par3 is the long-sought exocyst receptor required for targeted membrane-protein delivery.

MeSH Terms (23)

Animals Apoptosis Cadherins Cell Adhesion Molecules Cell Line Cell Polarity Cell Survival Enzyme Activation Epithelial Cells Female Gene Knockdown Techniques Golgi Apparatus Humans Lysine Mammary Glands, Animal Models, Biological Phosphatidylinositol Phosphates Phosphorylation Protein Domains Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase rab GTP-Binding Proteins Vesicular Transport Proteins

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