Clathrin-coated endocytic tubules mediate rapid and selective protein absorption by lysosome-rich enterocytes

Abstract

In the digestive tract of neonatal mammals and in fish, lysosome-rich enterocytes (LREs) internalize dietary proteins and digest them intracellularly within a large lysosomal vacuole. Impaired LRE function leads to growth stunting and poor survival in zebrafish and mice. Previous work has shown that protein uptake relies on a scavenger receptor complex. However, how LREs can internalize proteins rapidly enough to support organismal growth is unclear. Here, using live and electron microscopy and genetic manipulations in zebrafish, we find that LREs contain apical micron-sized clathrin-coated endocytic tubules (ETs) that allow for the concentration and rapid internalization of soluble protein cargoes, while excluding resident apical membrane proteins. Dab2, an endocytic adaptor linking clathrin to scavenger receptors, controls the biogenesis and function of ETs by recruiting unconventional myosin Myo6 and by influencing dynamin activity. Our findings suggest that continuous pinching of vesicles from ETs allows for rapid, high-capacity internalization of dietary protein.