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Updated: Jun 22, 2026

Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
Published on: January 3, 2012
Endocytosis of cholera toxin by human enterocytes is developmentally regulated
Lei Lu1, Sameer Khan, Wayne Lencer
1Developmental Gastroenterology Laboratory, Massachusetts General Hospital, 114 16th St. (114-3503), Charlestown, MA 02129-4404, USA.
Insights
Immature intestinal cells excessively absorb cholera toxin (CT) via clathrin-mediated endocytosis, unlike adult cells. This uptake pathway is developmentally regulated, explaining infant susceptibility to CT-induced diarrhea.
Area of Science:
- Gastroenterology
- Cell Biology
- Pediatrics
Background:
- Secretory diarrheas, including cholera, are more severe in infants due to immature intestinal responses.
- Cholera toxin (CT) induces chloride secretion via cAMP in intestinal epithelia, driving pathogenesis.
- Previous studies indicated excessive CT action and developmental regulation in immature enterocytes.
Purpose of the Study:
- To investigate if enhanced endocytosis by immature enterocytes contributes to excessive CT secretory response.
- To determine if enterocyte endocytosis of CT is developmentally regulated.
Main Methods:
- Utilized specific inhibitors to differentiate endocytic pathways in mature and immature human enterocyte cell lines.
- Compared CT internalization mechanisms and rates between adult and infant enterocytes.
Main Results:
- CT internalization is reduced in adult enterocytes, primarily using caveolae/raft-mediated pathways.
- Immature enterocytes exhibit enhanced CT uptake via a clathrin-mediated endocytosis pathway.
- Corticosteroids, a maturation factor, decreased CT endocytosis in immature enterocytes, indicating developmental regulation of the clathrin pathway.
Conclusions:
- Enhanced clathrin-mediated endocytosis in immature enterocytes contributes to increased CT uptake and secretory response.
- Enterocyte endocytosis of CT is developmentally regulated, with maturation reducing toxin internalization.
- Understanding these pathways offers insights into infant susceptibility to cholera and other secretory diarrheas.
Abstract:
Many secretory diarrheas including cholera are more prevalent and fulminant in young infants than in older children and adults. Cholera toxin (CT) elicits a cAMP-dependent chloride secretory response in intestinal epithelia, which accounts for the fundamental pathogenesis of this toxigenic diarrhea. We have previously reported that the action of this bacterial enterotoxin is excessive in immature enterocytes and under developmental regulation. In this study, we tested the hypothesis that enhanced endocytosis by immature human enterocytes may, in part, account for the excessive secretory response to CT noted in the immature intestine and that enterocyte endocytosis of CT is developmentally regulated. To test this hypothesis, we used specific inhibitors to define endocytic pathways in mature and immature cell lines. We showed that internalization of CT in adult enterocytes is less and occurs via the caveolae/raft-mediated pathway in contrast to an enhanced immature human enterocyte CT uptake that occurs via a clathrin pathway. We also present evidence that this clathrin pathway is developmentally regulated as demonstrated by its response to corticosteroids, a known maturation factor that causes a decreased CT endocytosis by this pathway.
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