ArticleCell stem cell2019
RAL GTPases Drive Intestinal Stem Cell Function and Regeneration through Internalization of WNT Signalosomes.
Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 65 citations in OpenAlex.
- G12 mutations rewire allosteric communication at the Ras-RalGDS interface.Biophysical journal · 2026Article
- RalGAP complexes control secretion and primary cilia in pancreatic disease.Life science alliance · 2025Article
- Metabolic regulation of intestinal homeostasis: molecular and cellular mechanisms and diseases.MedComm · 2024Review
- Advanced Progression for the Heterogeneity and Homeostasis of Intestinal Stem Cells.Stem cell reviews and reports · 2023Review
- Different congenital hydrocephalus-associated mutations in Trim71 impair stem cell differentiation via distinct gain-of-function mechanisms.PLoS biology · 2023Article
- Clone wars: From molecules to cell competition in intestinal stem cell homeostasis and disease.Experimental & molecular medicine · 2022Review
- Review
- Endocytosis at the Crossroad of Polarity and Signaling Regulation: Learning fromInternational journal of molecular sciences · 2022Review
- Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state.Theranostics · 2022Article
- The role of intestinal stem cell within gut homeostasis: Focusing on its interplay with gut microbiota and the regulating pathways.International journal of biological sciences · 2022Review
- Rlip Protein: A Potential Target for COVID-19.Journal of community hospital internal medicine perspectives · 2022Article
- Proliferation in the developing intestine is regulated by the endosomal protein Endotubin.Developmental biology · 2021Article
- Article
- Analysis of Ras-effector interaction competition in large intestine and colorectal cancer context.Small GTPases · 2021Article
- Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis in Drosophila.Nature cell biology · 2021Article
- ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Wnt/β-catenin signaling: Structure, assembly and endocytosis of the signalosome.Development, growth & differentiation · 2021Review
- Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage.Cell communication and signaling : CCS · 2021Review
- Ageing, metabolism and the intestine.EMBO reports · 2020Review
- Targeting Wnt Signaling for the Treatment of Gastric Cancer.International journal of molecular sciences · 2020Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Ral GTPases are RAS effector molecules and by implication a potential therapeutic target for RAS mutant cancer. However, very little is known about their roles in stem cells and tissue homeostasis. Using Drosophila, we identified expression of RalA in intestinal stem cells (ISCs) and progenitor cells of the fly midgut. RalA was required within ISCs for efficient regeneration downstream of Wnt signaling. Within the murine intestine, genetic deletion of either mammalian ortholog, Rala or Ralb, reduced ISC function and Lgr5 positivity, drove hypersensitivity to Wnt inhibition, and impaired tissue regeneration following damage. Ablation of both genes resulted in rapid crypt death. Mechanistically, RALA and RALB were required for efficient internalization of the Wnt receptor Frizzled-7. Together, we identify a conserved role for RAL GTPases in the promotion of optimal Wnt signaling, which defines ISC number and regenerative potential.
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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 OpenQuestion graph.