PUBLICATION
Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut
- Authors
- 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.
- ID
- ZDB-PUB-190903-3
- 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
- Datasets
- 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
Citation
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. (2019) Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut. Developmental Cell. 51(1):7-20.e6.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping