Evidence map›Paper›PMID 26015543›Full record

ArticleDevelopment (Cambridge, England)2015

Rab8a vesicles regulate Wnt ligand delivery and Paneth cell maturation at the intestinal stem cell niche.

Soumyashree Das, Shiyan Yu, Ryotaro Sakamori, Pavan Vedula, Qiang Feng, Juan Flores, Andrew Hoffman, Jiang Fu, Ewa Stypulkowski, Alexis Rodriguez and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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

38 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Water channel protein AQP1 in cytoplasm is a critical factor in breast cancer local invasion.Journal of experimental & clinical cancer research : CR · 2023
    Article
  6. The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. The Emerging Mechanisms of Wnt Secretion and Signaling in Development.Frontiers in cell and developmental biology · 2021
    Review
  18. LRPs in WNT Signalling.Handbook of experimental pharmacology · 2021
    Review
  19. Review
  20. Article
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

16 authors at 4 institutions in 2 countries.

Soumyashree DasDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Shiyan YuDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Ryotaro SakamoriDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Pavan VedulaDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Qiang FengDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Juan FloresDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Andrew HoffmanDepartment of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA.
Jiang FuDepartment of Biomedical Genetics, Center for Oral Biology, James P. Wilmot Cancer Center, Stem Cell and Regenerative Medicine Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
Ewa StypulkowskiDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Alexis RodriguezDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Radek DobrowolskiDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Akihiro HaradaDepartment of Cell Biology, Graduate School of Medicine, Osaka University 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
Wei HsuDepartment of Biomedical Genetics, Center for Oral Biology, James P. Wilmot Cancer Center, Stem Cell and Regenerative Medicine Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
Edward M BonderDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Michael P VerziDepartment of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Nan GaoDepartment of Biological Sciences, Rutgers University, Newark, NJ 07102, USA Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA ngao@andromeda.rutgers.edu.
Rutgers, The State University of New Jersey · USUniversity of Rochester Medical Center · USOsaka University · JPRutgers Cancer Institute of New Jersey

Funding

GENETIC REGULATORY NETWORK IN CRANIOFACIAL DEVELOPMENTR01DE015654 · NIDCR · UNIVERSITY OF ROCHESTER · PI Wei Hsu · 2006 to 2026
$8.2M
Genetic Regulatory Network in Mammary TumorigenesisR01CA106308 · NCI · UNIVERSITY OF ROCHESTER · PI HSU, WEI · 2004 to 2014
$3.1M
Endosomal Control of Microbe-Host HomeostasisR01DK102934 · NIDDK · RUTGERS THE STATE UNIV OF NJ NEWARK · PI GAO, NAN · 2014 to 2018
$1.8M
Transcriptional Regulation of the Intestinal EpitheliumK01DK088868 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI VERZI, MICHAEL P. · 2010 to 2014
$740k
Regulation of Apical-Basal Cell polarity during Intestinal Epithelial MorphogenesK01DK085194 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GAO, NAN · 2010 to 2014
$728k
Abrogating a survival pathway in early colon cancer cellsR21CA178599 · NCI · RUTGERS THE STATE UNIV OF NJ NEWARK · PI GAO, NAN · 2013 to 2014
$366k
Mechanisms underlying YY1 control of intestinal epithelial homeostasisR03DK099251 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI VERZI, MICHAEL P. · 2013 to 2014
$155k
The Division and Homeostasis of Gut Progenitor CellsR03DK093809 · NIDDK · RUTGERS THE STATE UNIV OF NJ NEWARK · PI GAO, NAN · 2012 to 2013
$152k
NCI NIH HHS CA106308NCI NIH HHS CA178599NCI NIH HHS R01 CA106308NCI NIH HHS R21 CA178599NIDCR NIH HHS DE015654NIDCR NIH HHS R01 DE015654NIDDK NIH HHS DK085194NIDDK NIH HHS DK088868NIDDK NIH HHS DK093809NIDDK NIH HHS DK099251NIDDK NIH HHS DK102934NIDDK NIH HHS K01 DK085194NIDDK NIH HHS K01 DK088868NIDDK NIH HHS R01 DK102934NIDDK NIH HHS R03 DK093809NIDDK NIH HHS R03 DK099251
6 · The paper itself

Abstract

Communication between stem and niche supporting cells maintains the homeostasis of adult tissues. Wnt signaling is a crucial regulator of the stem cell niche, but the mechanism that governs Wnt ligand delivery in this compartment has not been fully investigated. We identified that Wnt secretion is partly dependent on Rab8a-mediated anterograde transport of Gpr177 (wntless), a Wnt-specific transmembrane transporter. Gpr177 binds to Rab8a, depletion of which compromises Gpr177 traffic, thereby weakening the secretion of multiple Wnts. Analyses of generic Wnt/β-catenin targets in Rab8a knockout mouse intestinal crypts indicate reduced signaling activities; maturation of Paneth cells - a Wnt-dependent cell type - is severely affected. Rab8a knockout crypts show an expansion of Lgr5(+) and Hopx(+) cells in vivo. However, in vitro, the knockout enteroids exhibit significantly weakened growth that can be partly restored by exogenous Wnts or Gsk3β inhibitors. Immunogold labeling and surface protein isolation identified decreased plasma membrane localization of Gpr177 in Rab8a knockout Paneth cells and fibroblasts. Upon stimulation by exogenous Wnts, Rab8a-deficient cells show ligand-induced Lrp6 phosphorylation and transcriptional reporter activation. Rab8a thus controls Wnt delivery in producing cells and is crucial for Paneth cell maturation. Our data highlight the profound tissue plasticity that occurs in response to stress induced by depletion of a stem cell niche signal.

Indexed as

Animalsbeta CateninCell ProliferationCells, CulturedGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHomeodomain ProteinsHumansIntracellular Signaling Peptides and ProteinsLow Density Lipoprotein Receptor-Related Protein-6MiceMice, KnockoutPaneth CellsPhosphorylationrab GTP-Binding ProteinsReceptors, G-Protein-Coupledbeta CateninGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGpr177 protein, mouseGSK3B protein, humanGsk3b protein, mouseHomeodomain ProteinsIntracellular Signaling Peptides and ProteinsLgr5 protein, mouseLow Density Lipoprotein Receptor-Related Protein-6Lrp6 protein, mouseRab8a protein, mouserab GTP-Binding ProteinsReceptors, G-Protein-CoupledWnt ProteinsGpr177Intestinal stem cellPaneth cellRab8aWntlessWnt secretion

Identifiers

PMID26015543
PMCPMC4483769
OpenAlexW2205187654

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.