ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2014
Myosin 5b loss of function leads to defects in polarized signaling: implication for microvillus inclusion disease pathogenesis and treatment.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes.The Biochemical journal · 2025Article
- Modeling the cell biology of monogenetic intestinal epithelial disorders.The Journal of cell biology · 2024Review
- Patient-derived enteroids provide a platform for the development of therapeutic approaches in microvillus inclusion disease.The Journal of clinical investigation · 2023Article
- Therapy Development for Microvillus Inclusion Disease using Patient-derived Enteroids.bioRxiv : the preprint server for biology · 2023Article
- Myosin Vb as a tumor suppressor gene in intestinal cancer.Oncogene · 2022Article
- Loss of Serum Glucocorticoid-Inducible Kinase 1 SGK1 Worsens Malabsorption and Diarrhea in Microvillus Inclusion Disease (MVID).Journal of clinical medicine · 2022Article
- Bioinformatics Analysis Reveals the Biomarker Value and Potential Mechanism of miR-675-3p in Gastric Cancer.Computational intelligence and neuroscience · 2022Article
- MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression.PLoS genetics · 2020Article
- Editing Myosin VB Gene to Create Porcine Model of Microvillus Inclusion Disease, With Microvillus-Lined Inclusions and Alterations in Sodium Transporters.Gastroenterology · 2020Article
- Glucocorticoids and myosin5b loss of function induce heightened PKA signaling in addition to membrane traffic defects.Molecular biology of the cell · 2019Article
- Recent advances in understanding and managing malabsorption: focus on microvillus inclusion disease.F1000Research · 2019Review
- MYO5B, STX3, and STXBP2 mutations reveal a common disease mechanism that unifies a subset of congenital diarrheal disorders: A mutation update.Human mutation · 2018Review
- Intestinal epithelial cell polarity defects in disease: lessons from microvillus inclusion disease.Disease models & mechanisms · 2018Review
- Trafficking Ion Transporters to the Apical Membrane of Polarized Intestinal Enterocytes.Cold Spring Harbor perspectives in biology · 2018Review
- The Endosomal Protein Endotubin Is Required for Enterocyte Differentiation.Cellular and molecular gastroenterology and hepatology · 2018Article
- Loss of Myosin Vb in colorectal cancer is a strong prognostic factor for disease recurrence.British journal of cancer · 2017Article
- Mechanisms of Cell Polarity-Controlled Epithelial Homeostasis and Immunity in the Intestine.Cold Spring Harbor perspectives in biology · 2017Review
- Identification of intestinal ion transport defects in microvillus inclusion disease.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Loss of MYO5B in mice recapitulates Microvillus Inclusion Disease and reveals an apical trafficking pathway distinct to neonatal duodenum.Cellular and molecular gastroenterology and hepatology · 2016Article
- The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders.Disease models & mechanisms · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Microvillus inclusion disease (MVID) is an autosomal recessive condition resulting in intractable secretory diarrhea in newborns due to loss-of-function mutations in myosin Vb (Myo5b). Previous work suggested that the apical recycling endosomal (ARE) compartment is the primary location for phosphoinositide-dependent protein kinase 1 (PDK1) signaling. Because the ARE is disrupted in MVID, we tested the hypothesis that polarized signaling is affected by Myo5b dysfunction. Subcellular distribution of PDK1 was analyzed in human enterocytes from MVID/control patients by immunocytochemistry. Using Myo5b knockdown (kd) in Caco-2BBe cells, we studied phosphorylated kinases downstream of PDK1, electrophysiological parameters, and net water flux. PDK1 was aberrantly localized in human MVID enterocytes and Myo5b-deficient Caco-2BBe cells. Two PDK1 target kinases were differentially affected: phosphorylated atypical protein kinase C (aPKC) increased fivefold and phosohoprotein kinase B slightly decreased compared with control. PDK1 redistributed to a soluble (cytosolic) fraction and copurified with basolateral endosomes in Myo5b kd. Myo5b kd cells showed a decrease in net water absorption that could be reverted with PDK1 inhibitors. We conclude that, in addition to altered apical expression of ion transporters, depolarization of PDK1 in MVID enterocytes may lead to aberrant activation of downstream kinases such as aPKC. The findings in this work suggest that PDK1-dependent signaling may provide a therapeutic target for treating MVID.
Indexed as
Identifiers
What Socratic holds
Registered trials
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.