Phosphatidylinositol Synthase regulates the polarized deposition of basement membrane components. Olivier Devergne, Trudi Schüpbach. Department of Molecular Biology, HHMI/Princeton University , Princeton, NJ.

   Epithelial cells are characterized by their polarized architecture that enables them to exert their varied functions in embryonic and adult organisms. Epithelia exhibit a profound apical-basal polarity that is manifested in the cytoplasmic and surface organization of individual cells. Loss of apical-basal polarity is often associated with tumor metastasis. The establishment and maintenance of polarity relies on the regulated transport of newly synthesized and recycled proteins to these specific domains. The basement membrane (BM), a specialized sheet of the extracellular matrix contacting the basal side of epithelial tissues, has a major role in the establishment and maintenance of epithelial cell polarity. However, little is known about how BM proteins themselves achieve a polarized distribution. An attractive model system for the study of epithelial structure and morphogenesis is the follicular epithelium, which envelops the germline during Drosophila oogenesis. To unravel the molecular mechanism regulating the polarized deposition of the BM, we previously performed a genetic screen in which we identified Crag, a DENN domain containing protein, as a regulator of polarized BM secretion (1). We recently isolated a new gene involved in this process, pis, encoding Phosphatidylinositol Synthase, which has a critical role in phosphatidylinositol 4,5-bisphosphate (PIP2) regeneration after its hydrolysis into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) by Phospholipase C (PLC). PIP2 regulates many cellular functions, such as intracellular trafficking and membrane and ion transport. Significantly, in follicular cells mutant for pis, BM components are secreted at the apical side of the epithelium leading to the formation of an apical BM. This defect is not generally observed in mutants affecting epithelial polarity. However, apical, junctional and basolateral polarity is not affected. Altogether, our data indicate a specific role for pis in the organization of epithelial architecture by regulating the polarized deposition of BM components. (1) Denef et al., 2008.