Characterization of Endosomes in Development Intestine

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EXCEED THE SPACE PROVIDED. During the development of the intestine, the absorptive cells go through a stage in which they arehighly specialized for endocytosis of macromolecules from the intestinal lumen. During this time (which, depending upon the species, may occur in utero or after birth) these cells contain an elaborate endosomal complex. Although this complex has been shown to be important in the sorting and selective transepithelial transport of growth factors that are critical for the development of the intestine and other organ systems, little is known about the cellular mechanisms that allow for this selective transepithelial transport while antigens and pathogens are prevented from utilizing the same route. To identify the mechanisms that underlie selective transport, it is necessary to characterize the compartment involved in sorting of internalized macromolecules. We will utilize endotubin, an apical endosomal protein of the developing intestine, to define the molecular machinery involved in sorting in this endosomal compartment. The goals of the current proposal are to 1) identify molecules involved in sorting of apical endosomal proteins, 2) define the role of phosphorylation in the endocytosis and recycling of endotubin, 3) analyze the effect of disruption of endotubin expression on enterocyte development. This investigation of endosomal structure and regulation will provide insight into the molecular machinery important for epithelial cell function and the maintenance of epithelial polarity. In the long term, these studies will provide insight into the mechanism of sorting and targeting of developmentally important ligands such as growth factors. In addition, since the ability of the epithelial cells to selectively exclude antigens or pathogens is also critical to normal function, it is crucial that we understand the mechanisms of this process. Understanding the mechanisms of selective transepithelial transport will enhance our understanding of the intestinal barrier and provide strategies for the prevention of opportunistic infection and inappropriate antigen transport. PERFORMANCE SITE ========================================Section End===========================================