ArticleJournal of cell science2017
A Wntless-SEC12 complex on the ER membrane regulates early Wnt secretory vesicle assembly and mature ligand export.
Article in Journal of cell science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Wntless degradation mediated by CaMKII inhibition drives endoplasmic reticulum stress and apoptosis.Cell reports · 2026Article
- Wnt ligands in breast cancer metastasis: unraveling their dual roles and therapeutic potential.Molecular biology reports · 2026Review
- Beyond Vesicular Traffic: The ERES as the Gateway for Biosynthetic Secretion.Sub-cellular biochemistry · 2026Review
- Advances in the basic function of the small GTPase SAR1B and its regulatory role in the biological behavior of tumor cells (Review).Molecular and clinical oncology · 2026Review
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Ehbp1 orchestrates orderly sorting of Wnt/Wingless to the basolateral and apical cell membranes.EMBO reports · 2024Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Cryo-EM structure of human Wntless in complex with Wnt3a.Nature communications · 2021Article
- Ghrelin octanoylation by ghrelinOpen biology · 2021Review
- The Emerging Mechanisms of Wnt Secretion and Signaling in Development.Frontiers in cell and developmental biology · 2021Review
- Extracellular WNTs: Trafficking, Exosomes, and Ligand-Receptor Interaction.Handbook of experimental pharmacology · 2021Review
- Article
- Wntless regulates lipogenic gene expression in adipocytes and protects against diet-induced metabolic dysfunction.Molecular metabolism · 2020Article
- High levels of ubidecarenone (oxidized CoQScientific reports · 2020Article
- Export Control: Post-transcriptional Regulation of the COPII Trafficking Pathway.Frontiers in cell and developmental biology · 2020Review
- TMEM132A, a Novel Wnt Signaling Pathway Regulator Through Wntless (WLS) Interaction.Frontiers in cell and developmental biology · 2020Article
- Receptor-mediated endocytosis generates nanomechanical force reflective of ligand identity and cellular property.Journal of cellular physiology · 2018Article
- Wls Expression Correlates with Tumor Differentiation and TNM Stage in Hepatocellular Carcinoma.Digestive diseases and sciences · 2018Article
- Rab8 attenuates Wnt signaling and is required for mesenchymal differentiation into adipocytes.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Wntless (Wls) transports Wnt molecules for secretion; however, the cellular mechanism underlying the initial assembly of Wnt secretory vesicles is still not fully defined. Here, we performed proteomic and mutagenic analyses of mammalian Wls, and report a mechanism for formation of early Wnt secretory vesicles on ER membrane. Wls forms a complex with SEC12 (also known as PREB), an ER membrane-localized guanine nucleotide-exchange factor (GEF) activator of the SAR1 (the SAR1A isoform) small GTPase. Compared to palmitoylation-deficient Wnt molecules, binding of mature Wnt to Wls increases Wls-SEC12 interaction and promotes association of Wls with SAR1, the key activator of the COPII machinery. Incorporation of Wls into this exporting ER compartment is affected by Wnt ligand binding and SEC12 binding to Wls, as well as the structural integrity and, potentially, the folding of the cytosolic tail of Wls. In contrast, Wls-SEC12 binding is stable, with the interacting interface biochemically mapped to cytosolic segments of individual proteins. Mutant Wls that fails to communicate with the COPII machinery cannot effectively support Wnt secretion. These data suggest that formation of early Wnt secretory vesicles is carefully regulated to ensure proper export of functional ligands.
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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.