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

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  • Syed Mukhtar Ahmed

    (Vanderbilt University School of Medicine)

  • Ian G. Macara

    (Vanderbilt University School of Medicine)

Abstract

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.

Suggested Citation

  • Syed Mukhtar Ahmed & Ian G. Macara, 2017. "The Par3 polarity protein is an exocyst receptor essential for mammary cell survival," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14867
    DOI: 10.1038/ncomms14867
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    1. Kaori Kanemaru & Makoto Shimozawa & Manabu Kitamata & Rikuto Furuishi & Hinako Kayano & Yui Sukawa & Yuuki Chiba & Takatsugu Fukuyama & Junya Hasegawa & Hiroki Nakanishi & Takuma Kishimoto & Kazuya Ts, 2022. "Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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