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Regulation of Polarized Biosynthetic Traffic by Phosphatidylinositol Metabolizing Enzymes

 

The local generation of distinct phosphatidylinositol (PI) lipid species has been implicated in the regulation of numerous membrane trafficking events and in the control of cytoskeletal dynamics. The compartmentalized synthesis of PIs is critical for cells to control multiple PI-dependent functions independently. Our long term goal is to understand how localized PI synthesis regulates polarized membrane traffic in normal and disease states. Currently, we are exploring the mechanisms by which polarized biosynthetic and endocytic membrane traffic is modulated by PI metabolizing enzymes.

We have found that apical and basolateral biosynthetic and endocytic pathways are differentially sensitive to changes in cellular PIs. Surface delivery of a subset of apical proteins is regulated by phosphatidylinositol 4,5-bisphosphate (PIP 2 ) via a mechanism involving the modulation of actin dynamics. We are currently working to understand the role of differentially localized PI 5-kinases in polarized endocytosis. In addition, we are exploring whether acute modulation of surface PIP 2 levels in response to physiological stimuli can serve as a mechanism to modulate endocytic efficiency.

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