title: The Par3 polarity protein is an exocyst receptor essential for mammary cell survival.
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.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Syed Mukhtar
authors.identifier: 0000-0002-9183-9957
authors.initials: SM
authors.lastname: Ahmed
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D016764:Cell Polarity; D002470:Cell Survival; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology*; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D000072417:Protein Domains; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D008239:Lysine; D051059:PTEN Phosphohydrolase; D018129:Phosphatidylinositol Phosphates; D051057:Proto-Oncogene Proteins c-akt; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C115084:Pard3 protein, mouse; C060974:phosphatidylinositol 3,4,5-triphosphate