Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Amy C. Engevik, Izumi Kaji, Meagan M. Postema, James J. Faust, Anne R. Meyer, Janice A. Williams, Gillian N. Fitz, Matthew J. Tyska, Jean M. Wilson, James R. Goldenring

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

In patients with inactivating mutations in myosin Vb (Myo5B), enterocytes show large inclusions lined by microvilli. The origin of inclusions in small-intestinal enterocytes in microvillus inclusion disease is currently unclear. We postulated that inclusions in Myo5b KO mouse enterocytes form through invagination of the apical brush border membrane. 70-kD FITC-dextran added apically to Myo5b KO intestinal explants accumulated in intracellular inclusions. Live imaging of Myo5b KO-derived enteroids confirmed the formation of inclusions from the apical membrane. Treatment of intestinal explants and enteroids with Dyngo resulted in accumulation of inclusions at the apical membrane. Inclusions in Myo5b KO enterocytes contained VAMP4 and Pacsin 2 (Syndapin 2). Myo5b;Pacsin 2 double-KO mice showed a significant decrease in inclusion formation. Our results suggest that apical bulk endocytosis in Myo5b KO enterocytes resembles activity-dependent bulk endocytosis, the primary mechanism for synaptic vesicle uptake during intense neuronal stimulation. Thus, apical bulk endocytosis mediates the formation of inclusions in neonatal Myo5b KO enterocytes.

Original languageEnglish (US)
Pages (from-to)3647-3662
Number of pages16
JournalJournal of Cell Biology
Volume218
Issue number11
DOIs
StatePublished - Nov 4 2019

ASJC Scopus subject areas

  • Cell Biology

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    Engevik, A. C., Kaji, I., Postema, M. M., Faust, J. J., Meyer, A. R., Williams, J. A., Fitz, G. N., Tyska, M. J., Wilson, J. M., & Goldenring, J. R. (2019). Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes. Journal of Cell Biology, 218(11), 3647-3662. https://doi.org/10.1083/JCB.201902063