Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut.
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
Intestinal Absorption
Intestines
/ embryology
Kwashiorkor
/ metabolism
Ligands
Lysosomes
/ metabolism
Male
Membrane Proteins
/ metabolism
Mice
Receptors, Cell Surface
/ metabolism
Zebrafish
Zebrafish Proteins
/ metabolism
Cubilin
Dab2
inter-organ transport
intestine
kwashiorkor
lysosome-rich enterocytes (LREs)
malnutrition
mouse
protein absorption
zebrafish
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
07 10 2019
07 10 2019
Historique:
received:
31
03
2019
revised:
06
06
2019
accepted:
29
07
2019
pubmed:
3
9
2019
medline:
28
5
2020
entrez:
3
9
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31474562
pii: S1534-5807(19)30661-6
doi: 10.1016/j.devcel.2019.08.001
pmc: PMC6783362
mid: NIHMS1537093
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Adaptor Proteins, Vesicular Transport
0
Amn protein, mouse
0
Apoptosis Regulatory Proteins
0
Dab2 protein, mouse
0
Dab2 protein, zebrafish
0
Dietary Proteins
0
Ligands
0
Membrane Proteins
0
Receptors, Cell Surface
0
Zebrafish Proteins
0
intrinsic factor-cobalamin receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7-20.e6Subventions
Organisme : NIDDK NIH HHS
ID : P01 DK094779
Pays : United States
Organisme : NIDDK NIH HHS
ID : F31 DK111137
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK081426
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117981
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113123
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR055926
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007568
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR067203
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121007
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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