Evidence mapPaperPMID 39299401Full record

ArticleGastroenterology2025

Myosin Vb Traffics P-Glycoprotein to the Apical Membrane of Intestinal Epithelial Cells.

Sarah A Dooley, Elena Kolobova, Andreanna Burman, Izumi Kaji, Jessica R Digrazia, Rachel Stubler, Anna Goldstein, Charulekha Packirisamy, Alexander W Coutts, Milena Saqui-Salces and 5 more

Abstract read
In one paragraph

Article in Gastroenterology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Sarah A DooleyDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
Elena KolobovaSection of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Andreanna BurmanSection of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Izumi KajiSection of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Jessica R DigraziaDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
Rachel StublerDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
Anna GoldsteinSection of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Charulekha PackirisamyDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina.
Alexander W CouttsRecombinetics, Inc, Eagan, Minnesota.
Milena Saqui-SalcesDepartment of Animal Science, University of Minnesota, Saint Paul, Minnesota.
Nan GaoDepartment of Pharmacology, Physiology, and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey.
Melinda A EngevikDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina.
Mitchell D ShubDivision of Gastroenterology, Phoenix Children's Hospital, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona.
James R GoldenringSection of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Nashville Veterans Affairs Medical Center, Nashville, Tennessee.
Amy C EngevikEpithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: engevika@musc.edu.

Funding

The Impact of p53 Variants on Liver DiseaseP20GM130457 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 to 2025
$10.2M
Translational Analysis CoreP30DK058404 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2002 to 2025
$4.9M
SMALL GTP BINDING PROTEINS IN GASTROINTESTINAL MUCOSAR01DK048370 · VANDERBILT UNIVERSITY MEDICAL CENTER · 1994 to 2025
$3.1M
COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$2.0M
Proteomics CoreP30DK123704 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$1.1M
Paneth cell heterogeneity in infection and inflammationR01DK132885 · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2025 to 2025
$468k
Impacting the pathophysiology of malabsorption induced by Myosin Vb inactivating mutationsR01DK128190 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$381k
Digestive Disease Training ProgramT32DK124191 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$213k
Elucidating the role of Myosin 5b in microvilli assembly and in the setting of inflammationF31DK139736 · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2025 to 2025
$45k
NIDDK NIH HHS F31 DK139736NIDDK NIH HHS K01 DK121869NIDDK NIH HHS P30 DK058404NIDDK NIH HHS P30 DK123704NIDDK NIH HHS R01 DK048370NIDDK NIH HHS R01 DK102934NIDDK NIH HHS R01 DK119198NIDDK NIH HHS R01 DK128190NIDDK NIH HHS R01 DK132885NIDDK NIH HHS R43 DK109820NIDDK NIH HHS RC2 DK118640NIDDK NIH HHS T32 DK124191NIGMS NIH HHS P20 GM130457
6 · The paper itself

Abstract

BACKGROUND &

aimsThe xenobiotic efflux pump P-glycoprotein is highly expressed on the apical membrane of the gastrointestinal tract, where it regulates the levels of intracellular substrates. P-glycoprotein is altered in disease, but the mechanisms that regulate the levels of P-glycoprotein are still being explored. The molecular motor myosin Vb (Myo5b) traffics diverse cargo to the apical membrane of intestinal epithelial cells. We hypothesized that Myo5b was responsible for the delivery of P-glycoprotein to the apical membrane of enterocytes.

methodsWe used multiple murine models that lack functional Myo5b or the myosin binding partner Rab11a to analyze P-glycoprotein localization. Pig and human tissue were analyzed to determine P-glycoprotein localization in the setting of MYO5B mutations. Intestinal organoids were used to examine P-glycoprotein trafficking and to assay P-glycoprotein function when MYO5 is inhibited.

resultsIn mice lacking Myo5b or the binding partner Rab11a, P-glycoprotein was improperly trafficked and had decreased presence in the brush border of enterocytes. Immunostaining of a pig model lacking functional Myo5b and human biopsies from a patient with an inactivating mutation in Myo5b also showed altered localization of intestinal P-glycoprotein. Human intestinal organoids expressing the motorless MYO5B tail domain had colocalization with P-glycoprotein, confirming that P-glycoprotein was trafficked by MYO5B in human enterocytes. Inhibition of MYO5 in human intestinal cell lines and organoids resulted in decreased P-glycoprotein capacity. Additionally, inhibition of MYO5 in human colon cancer cells diminished P-glycoprotein activity and increased cell death in response to a chemotherapeutic drug.

conclusionsCollectively, these data demonstrate that Myo5b is necessary for the apical delivery of P-glycoprotein.

Indexed as

EnterocytesMyosin Heavy ChainsMyosin Type Vrab GTP-Binding ProteinsAnimalsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Cell MembraneHumansIntestinal MucosaMiceMice, KnockoutMutationOrganoidsProtein Transportrab11 GTP-Binding ProteinsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1MYO5B protein, humanMyo5B protein, mouseMyosin Heavy ChainsMyosin Type Vrab11 GTP-Binding Proteinsrab GTP-Binding ProteinsCell TraffickingMDR1Myosin VbP-Glycoprotein

Identifiers

PMID39299401
PMCPMC11663138

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.