Lipid sorting and formation of distinct plasma membrane domains during cell polarization in Drosophila

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The sorting of plasma membrane components including proteins and lipids in the trans-Golgi network (TGN) into apical and basolateral transport vesicles and the correct delivery to surface domains are mechanisms by which cell polarity is maintained (1). However, they fail to explain how cell polarity is initially established and which role sorting mechanisms for proteins and lipids may play in this process. In addition, it is not understood whether distinct membrane compartments are established prior to or after formation of a membrane fence that blocks lateral lipid diffusion and what role such a fence may have for targeting mechanisms. Previous studies suggest a role of the endocytic pathway in polarized targeting of protein and lipid components (2,3,4). We want to test whether membrane trafficking along the endocytic and biosynthetic pathway monitored by fluorescent lipid analogs has pronounced effects on the establishment of cell polarity. We propose to test the effects on establishment and maintenance of cellular polarity by studying intracellular lipid transport and by gene inactivation of components of the endocytic pathway in Drosophila. Conversely, some genes for which a role in establishment of cell polarity has been ascribed may function in protein or lipid sorting as well. We will investigate this possibility by employing Drosophila mutants with defects in cellular polarity to characterize whether the existing targeting mechanisms may be affected. Finally, we will use the Drosophila genomic sequence and gene prediction programs to identify candidate transmembrane proteins with a possible role in establishing the membrane fence that separates apical from basolateral membrane compartments. The function of those candidate genes will be tested using existing mutants or RNA interference.