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
  • Ligands
  • Membrane Proteins/metabolism
  • Adaptor Proteins, Signal Transducing/metabolism
  • Gene Expression Regulation, Developmental
  • Gastrointestinal Microbiome
  • Lysosomes/metabolism*
  • Enterocytes/metabolism*
  • Zebrafish
  • Intestinal Absorption*
  • Apoptosis Regulatory Proteins/metabolism
  • Intestines/embryology*
  • Kwashiorkor/metabolism
  • Adaptor Proteins, Vesicular Transport/metabolism
  • Dietary Proteins/metabolism*
  • Disease Models, Animal
  • Receptors, Cell Surface/metabolism
  • Ileum/embryology
  • Ileum/metabolism
  • Zebrafish Proteins/metabolism
  • Animals
  • Gene Deletion
  • Mice
  • Male
  • Female
(all 24)
PubMed
31474562 Full text @ Dev. Cell
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
Figures
Figure Gallery (7 images)
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
amnpd1189/pd1189controlDay 6
cubnpd1169/pd1169controlDay 6
cubnpd1169/pd1169controlDays 30-44
cubnpd1169/pd1169low proteinDays 30-44
dab2pd1162/pd1162controlDay 6
dab2pd1162/pd1162controlDay 6
dab2pd1162/pd1162controlDays 7-13
dab2pd1162/pd1162controlDays 7-13
dab2pd1162/pd1162controlDays 7-13
dab2pd1162/pd1162controlDays 30-44
1 - 10 of 19
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
mw1
    		Point Mutation
    pd1034TgTransgenic Insertion
      pd1044TgTransgenic Insertion
        pd1046TgTransgenic Insertion
          pd1113TgTransgenic Insertion
            pd1142TgTransgenic Insertion
              pd1162
                		Small Deletion
                pd1169
                  		Small Deletion
                  pd1177TgTransgenic Insertion
                    pd1189
                      		Small Deletion
                      1 - 10 of 13
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      amnCRISPR1-amnCRISPR
                      cubnCRISPR1-cubnCRISPR
                      dab2CRISPR2-dab2CRISPR
                      1 - 3 of 3
                      Show
                      Fish
                      Fish
                      amnpd1189/pd1189
                      cubnpd1169/pd1169
                      dab2pd1162/pd1162
                      EKW
                      lrp2amw1/mw1
                      pd1034Tg
                      1 - 6 of 6
                      Show
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      FYVEEFGFYVE
                      GFPEFGGFP
                      mCherryEFGmCherry
                      QFEFGQF
                      RFPEFGRFP
                      VenusEFGVenus
                      1 - 7 of 7
                      Show
                      Mapping
                      No data available
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                      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.