Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Amy C Engevik1,2, Izumi Kaji1,2, Meagan M Postema2

  • 1Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN.

The Journal of Cell Biology
|September 29, 2019
PubMed

Insights

Inclusions in microvillus inclusion disease form via apical bulk endocytosis in myosin Vb (Myo5B) knockout enterocytes. This process involves invagination of the apical membrane, similar to synaptic vesicle uptake.

Area of Science:

  • Cell Biology
  • Gastroenterology
  • Molecular Medicine

Background:

  • Microvillus inclusion disease (MVID) is characterized by enterocyte inclusions, but their origin is unknown.
  • Inactivating mutations in myosin Vb (Myo5B) cause MVID, leading to enterocyte inclusions lined by microvilli.

Purpose of the Study:

  • To investigate the origin of intracellular inclusions in enterocytes of Myo5b knockout (KO) mice.

Main Methods:

  • Utilized Myo5b KO mouse intestinal explants and enteroids.
  • Applied live imaging and fluorescent dextran uptake assays.
  • Investigated the role of Pacsin 2 (Syndapin 2) in inclusion formation.

Main Results:

  • Confirmed inclusion formation from apical membrane invagination in Myo5b KO enterocytes.
  • Demonstrated that 70-kD FITC-dextran uptake into inclusions occurs apically.
  • Showed that inclusions contain VAMP4 and Pacsin 2, with double KO mice exhibiting reduced inclusion formation.

Conclusions:

  • Apical bulk endocytosis mediates inclusion formation in neonatal Myo5b KO enterocytes.
  • This mechanism resembles activity-dependent bulk endocytosis observed in neuronal tissues.
  • Findings elucidate the cellular basis of MVID pathogenesis.

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