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Polarity protein role in cell survival

by Laura Daniel

Cell survival is dependent upon regulation of numerous proteins, both cytosolic and membrane bound.

Reporting in Nature Communications, Mukhtar Ahmed, Ph.D., and Ian Macara, Ph.D., identified an unexpected link between cell survival and the polarized delivery of proteins to the surface of mammary epithelial cells.

The Par3 protein plays a central role in polarity. It is located near the tight junction at the basolateral side of epithelial cells. Prior to Ahmed and Macara’s work, Par3 had been implicated in cell death and proliferation; however, the mechanisms were unknown.

Proteins are delivered to the cell membrane in vesicles by an octameric complex or the exocyst that must “dock” on the plasma membrane to deliver its contents.

When Par3 was silenced, the exocyst was unable to dock. This caused defects in membrane protein deliveries and as a consequence decreased activity of the pro-survival, Akt signaling protein.

Their work suggests that Par3 is a novel, long-sought exocyst receptor and that this function is required for mammary epithelial cells.

This work was supported by an NIH/NIGMS grant (GM070902) and the Canadian Institutes of Health Research.

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