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.

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