Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes
AuthorEngevik, Amy C
Postema, Meagan M
Faust, James J
Meyer, Anne R
Williams, Janice A
Fitz, Gillian N
Tyska, Matthew J
Wilson, Jean M
Goldenring, James R
AffiliationUniv Arizona, Bio5 Inst, Dept Cellular & Mol Med
MetadataShow full item record
PublisherROCKEFELLER UNIV PRESS
CitationEngevik, A. C., Kaji, I., Postema, M. M., Faust, J. J., Meyer, A. R., Williams, J. A., ... & Goldenring, J. R. (2019). Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes. The Journal of Cell Biology, 218(11), 3647-3662.
JournalJOURNAL OF CELL BIOLOGY
RightsCopyright © 2019 Engevik et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractIn 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.
Note6 month embargo; published online: 27 September 2019
VersionFinal published version
SponsorsUnited States Department of Health & Human Services - National Institutes of Health (NIH) - USA [R01 DK48370, R01 DK70856, F32 DK111101, R01 DK111949, R01 DK095811, 1R01 DK109701]; Vanderbilt Digestive Disease Center [P30 DK058404]; Vanderbilt-Ingram Cancer Center [P30 CA68485]; Shared Equipment Grant - US Department of Veteran Affairs [1IS1BX003097]