Investigating Endocytic Mechanisms in Lysosome Rich Enterocytes

ABSTRACT Nutrient absorption in the neonatal mammalian gut relies on intracellular digestion by a population of enterocytes known as vacuolated or neonatal enterocytes. Recently, we showed these cells are conserved between zebrafish and mammals and are specialized in the uptake and digestion of dietary proteins. As these cells possess a prominent lysosomal vacuole and are present in non-mammalian vertebrates such as fish, we refer to them as Lysosome Rich Enterocytes (LREs). In our previous studies, we found that protein uptake in zebrafish and mouse LREs is mediated by a scavenger receptor complex composed of cubilin (Cubn), its transmembrane partner amnionless (Amn), and the endocytic adaptor Dab2. However, the cellular mechanisms that allow LREs to internalize cargo from the intestinal lumen at an astounding rate are unknown. Here, we will leverage the experimental advantages of the zebrafish system and the conserved biology of LREs to investigate the endocytic machinery that allows these cells to support dietary protein absorption in the intestine. Specifically, we will elucidate the mechanisms regulating a specialized form of clathrin mediated endocytosis that confers LREs a high capacity for luminal protein uptake.