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

doi:10.1083/JCB.201902063

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 journal › Article › peer-review

15 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 language	English (US)
Pages (from-to)	3647-3662
Number of pages	16
Journal	Journal of Cell Biology
Volume	218
Issue number	11
DOIs	https://doi.org/10.1083/JCB.201902063
State	Published - Nov 4 2019

ASJC Scopus subject areas

Cell Biology

Access to Document

10.1083/JCB.201902063

Cite this

@article{dbf305d583cc4f7ba6d8d0abf9362d2c,

title = "Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019 Engevik et al.",

year = "2019",

month = nov,

day = "4",

doi = "10.1083/JCB.201902063",

language = "English (US)",

volume = "218",

pages = "3647--3662",

journal = "Journal of Cell Biology",

issn = "0021-9525",

publisher = "Rockefeller University Press",

number = "11",

}

TY - JOUR

T1 - Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

AU - Engevik, Amy C.

AU - Kaji, Izumi

AU - Postema, Meagan M.

AU - Faust, James J.

AU - Meyer, Anne R.

AU - Williams, Janice A.

AU - Fitz, Gillian N.

AU - Tyska, Matthew J.

AU - Wilson, Jean M.

AU - Goldenring, James R.

PY - 2019/11/4

Y1 - 2019/11/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85074551940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074551940&partnerID=8YFLogxK

U2 - 10.1083/JCB.201902063

DO - 10.1083/JCB.201902063

M3 - Article

C2 - 31562230

SN - 0021-9525

VL - 218

SP - 3647

EP - 3662

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 11

ER -

Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this