MOLECULAR STRUCTURE OF ENDOSOMES IN DEVELOPING INTESTINE

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DESCRIPTION: This is a renewal application to continue to study the development of absorptive function within the gastrointestinal tract in the neonatal rat. The enterocyte during early neonatal period has an elaborate endosomal system that has the capacity to endocytosis increase quantities of macromolecules. The intestinal tract also has a capacity for these engulfed vesicles to selectively transport physiologic molecules such as growth factors and hormones through the cell without disruption and either act directly on the cell or extended intact from the basolateral membrane. Alternatively, the enterocyte can function as a mucosal barrier to prevent the uptake of pathologic antigens and micro-organisms. The principal investigator has identified a molecule, endotubin, which is a specific protein present in the developing intestine within the apical endosome and can be used as a marker to define the function of apical endosomes in the developing intestine and to determine the process by which the endosome functions within the gastrointestinal tract. The goals of this current proposal, having cloned the endotubin DNA and identified its effect on non-polarized and polarized cell, is to: 1) identify the targeting signals involved in the biogenesis of specialized endosomes. 2) to define endocytosis and recycling through this compartment. 3) to isolate new endosomal proteins. 4) to map the chromosome localization of the human endotubin gene within the human genome. If these goals are accomplished, a better understanding of the importance of the epithelium as a barrier to the luminal environment will be forthcoming and ways to use the endosomal trafficking pattern appropriately in the delivery of either antibodies or physiologic molecules can be better understood.