ArticleCirculation research2012
LRP1-dependent endocytic mechanism governs the signaling output of the bmp system in endothelial cells and in angiogenesis.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer.International journal of molecular sciences · 2021Trial
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- Inhibition of BMPER Mitigates Pulmonary Hypertension by Modulating LRP1-YAP Interaction in Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- LRP1 Mediates Endocytosis Activity and Is a Potential Therapeutic Target in Osteoarthritis.Orthopaedic surgery · 2025Review
- Cerebral Vascular Toxicity after Developmental Exposure to Arsenic (As) and Lead (Pb) Mixtures.Toxics · 2024Article
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- GPR126 is a specifier of blood-brain barrier formation in the mouse central nervous system.The Journal of clinical investigation · 2024Article
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- BMPER Improves Vascular Remodeling and the Contractile Vascular SMC Phenotype.International journal of molecular sciences · 2023Article
- The endocytic receptor protein LRP-1 modulate P-glycoprotein mediated drug resistance in MCF-7 cells.PloS one · 2023Article
- Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension.JACC. Basic to translational science · 2022Review
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- Dual drug delivery platforms for bone tissue engineering.Frontiers in bioengineering and biotechnology · 2022Review
- Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.Nature communications · 2021Article
- Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment.Biology open · 2021Article
- Loss of bone morphogenetic protein-binding endothelial regulator causes insulin resistance.Nature communications · 2021Article
- The Dual Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Atherosclerosis.Frontiers in cardiovascular medicine · 2021Review
- Novel Ethanol-Sensitive Mutants Identified in an F3 Forward Genetic Screen.Alcoholism, clinical and experimental research · 2020Article
- Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Is a Negative Regulator of Oligodendrocyte Progenitor Cell Differentiation in the Adult Mouse Brain.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleAmong the extracellular modulators of Bmp (bone morphogenetic protein) signaling, Bmper (Bmp endothelial cell precursor-derived regulator) both enhances and inhibits Bmp signaling. Recently we found that Bmper modulates Bmp4 activity via a concentration-dependent, endocytic trap-and-sink mechanism.
objectiveTo investigate the molecular mechanisms required for endocytosis of the Bmper/Bmp4 and signaling complex and determine the mechanism of Bmper's differential effects on Bmp4 signaling. METHODS AND
resultsUsing an array of biochemical and cell biology techniques, we report that LRP1 (LDL receptor-related protein 1), a member of the LDL receptor family, acts as an endocytic receptor for Bmper and a coreceptor of Bmp4 to mediate the endocytosis of the Bmper/Bmp4 signaling complex. Furthermore, we demonstrate that LRP1-dependent Bmper/Bmp4 endocytosis is essential for Bmp4 signaling, as evidenced by the phenotype of lrp1-deficient zebrafish, which have abnormal cardiovascular development and decreased Smad1/5/8 activity in key vasculogenic structures.
conclusionsTogether, these data reveal a novel role for LRP1 in the regulation of Bmp4 signaling by regulating receptor complex endocytosis. In addition, these data introduce LRP1 as a critical regulator of vascular development. These observations demonstrate Bmper's ability to fine-tune Bmp4 signaling at the single-cell level, unlike the spatial regulatory mechanisms applied by other Bmp modulators.
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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.