ArticleProceedings of the National Academy of Sciences of the United States of America2012
Multistep molecular mechanism for bone morphogenetic protein extracellular transport in the Drosophila embryo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Shrew is an essential, recently evolved, Drosophila specific gene required for formation of the embryonic BMP activity gradient.Developmental biology · 2026Article
- Development of a diagnostic model for ovarian cancer based on machine learning algorithms and functional analysis of key biomarker SOX17.Journal of ovarian research · 2025Article
- Receptor binding and tortuosity explain morphogen local-to-global diffusion coefficient transition.Biophysical journal · 2025Article
- Digital cousins: Simultaneous optimization of one model for BMP signaling in distant relatives reveals essential core.Computational and structural biotechnology journal · 2025Article
- Molecular mechanism of BMP signal control by Twisted gastrulation.Nature communications · 2024Article
- Review
- A prognostic model based on regulatory T-cell-related genes in gastric cancer: Systematic construction and validation.International journal of experimental pathology · 2023Article
- Modelling the structure of Short Gastrulation and generation of a toolkit for studying its function in Drosophila.Biology open · 2022Article
- Article
- Article
- BMP antagonists in tissue development and disease.Matrix biology plus · 2021Review
- Diversity and robustness of bone morphogenetic protein pattern formation.Development (Cambridge, England) · 2021Review
- Feedback regulation of BMP signaling byMolecular biology of the cell · 2020Article
- The calcium channel subunit αNature communications · 2019Article
- Coacting enhancers can have complementary functions within gene regulatory networks and promote canalization.PLoS genetics · 2019Article
- N-linked glycosylation restricts the function of Short gastrulation to bind and shuttle BMPs.Development (Cambridge, England) · 2018Article
- A novel scoring system for gastric cancer risk assessment based on the expression of three CLIP4 DNA methylation-associated genes.International journal of oncology · 2018Article
- Building collagen IV smart scaffolds on the outside of cells.Protein science : a publication of the Protein Society · 2017Review
- TGF-β Family Signaling inCold Spring Harbor perspectives in biology · 2017Review
- Control of signaling molecule range during developmental patterning.Cellular and molecular life sciences : CMLS · 2017Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In the Drosophila embryo, formation of a bone morphogenetic protein (BMP) morphogen gradient requires transport of a heterodimer of the BMPs Decapentaplegic (Dpp) and Screw (Scw) in a protein shuttling complex. Although the core components of the shuttling complex--Short Gastrulation (Sog) and Twisted Gastrulation (Tsg)--have been identified, key aspects of this shuttling system remain mechanistically unresolved. Recently, we discovered that the extracellular matrix protein collagen IV is important for BMP gradient formation. Here, we formulate a molecular mechanism of BMP shuttling that is catalyzed by collagen IV. We show that Dpp is the only BMP ligand in Drosophila that binds collagen IV. A collagen IV binding-deficient Dpp mutant signals at longer range in vivo, indicating that collagen IV functions to immobilize free Dpp in the embryo. We also provide in vivo evidence that collagen IV functions as a scaffold to promote shuttling complex assembly in a multistep process. After binding of Dpp/Scw and Sog to collagen IV, protein interactions are remodeled, generating an intermediate complex in which Dpp/Scw-Sog is poised for release by Tsg through specific disruption of a collagen IV-Sog interaction. Because all components are evolutionarily conserved, we propose that regulation of BMP shuttling and immobilization through extracellular matrix interactions is widely used, both during development and in tissue homeostasis, to achieve a precise extracellular BMP distribution.
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