ZFIN ID: ZDB-PUB-190903-3
Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut
Park, J., Levic, D.S., Sumigray, K.D., Bagwell, J., Eroglu, O., Block, C.L., Eroglu, C., Barry, R., Lickwar, C.R., Rawls, J.F., Watts, S.A., Lechler, T., Bagnat, M.
Date: 2019
Source: Developmental Cell   51(1): 7-20.e6 (Journal)
Registered Authors: Bagnat, Michel, Lickwar, Colin, Rawls, John F.
Keywords: Cubilin, Dab2, inter-organ transport, intestine, kwashiorkor, lysosome-rich enterocytes (LREs), malnutrition, mouse, protein absorption, zebrafish
Microarrays: GEO:GSE124970
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/metabolism
  • Adaptor Proteins, Vesicular Transport/metabolism
  • Animals
  • Apoptosis Regulatory Proteins/metabolism
  • Dietary Proteins/metabolism*
  • Disease Models, Animal
  • Enterocytes/metabolism*
  • Female
  • Gastrointestinal Microbiome
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Ileum/embryology
  • Ileum/metabolism
  • Intestinal Absorption*
  • Intestines/embryology*
  • Kwashiorkor/metabolism
  • Ligands
  • Lysosomes/metabolism*
  • Male
  • Membrane Proteins/metabolism
  • Mice
  • Receptors, Cell Surface/metabolism
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 31474562 Full text @ Dev. Cell
The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is still immature is unknown. Here, we show that specialized intestinal cells, which we call lysosome-rich enterocytes (LREs), internalize dietary protein via receptor-mediated and fluid-phase endocytosis for intracellular digestion and trans-cellular transport. In LREs, we identify a conserved endocytic machinery, composed of the scavenger receptor complex Cubilin/Amnionless and Dab2, that is required for protein uptake by LREs and for growth and survival of larval zebrafish. Moreover, impairing LRE function in suckling mice, via conditional deletion of Dab2, leads to stunted growth and severe protein malnutrition reminiscent of kwashiorkor, a devastating human malnutrition syndrome. These findings identify digestive functions and conserved molecular mechanisms in LREs that are crucial for vertebrate growth and survival.