ArticleThe Journal of biological chemistry2013
Molecular mediators for raft-dependent endocytosis of syndecan-1, a highly conserved, multifunctional receptor.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 76 citations in OpenAlex.
- DHRS2 regulates epithelial-mesenchymal transition in breast cancer cells.Molecular biology reports · 2026Article
- Tumour acidosis remodels the glycocalyx to control lipid scavenging and ferroptosis.Nature cell biology · 2026Article
- Endocytic Pathways Unveil the Role of Syndecans in the Seeding and Spreading of Pathological Protein Aggregates: Insights into Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- The transmembrane protein Syndecan is required for stem cell survival and maintenance of their nuclear properties.PLoS genetics · 2025Article
- The Pivotal Role of Irradiation-induced Autophagy Mechanisms in Glioma Therapy.Anti-cancer agents in medicinal chemistry · 2025Review
- SDC1-dependent TGM2 determines radiosensitivity in glioblastoma by coordinating EPG5-mediated fusion of autophagosomes with lysosomes.Autophagy · 2023Article
- Dynamic changes in the glycocalyx and clinical outcomes in patients undergoing endovascular treatments for large vessel occlusion.Frontiers in neurology · 2023Article
- Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice.International journal of molecular sciences · 2022Article
- Targeting syndecan-1: new opportunities in cancer therapy.American journal of physiology. Cell physiology · 2022Review
- Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke.Brain pathology (Zurich, Switzerland) · 2022Article
- Promising Antigens for the New Frontier of Targeted Immunotherapy in Multiple Myeloma.Cancers · 2021Review
- Investigation of the invasion mechanism mediated by the outer membrane protein PagN of Salmonella Typhimurium.BMC microbiology · 2021Article
- Syndecan-1 (CD138), Carcinomas and EMT.International journal of molecular sciences · 2021Review
- Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.Seminars in thrombosis and hemostasis · 2021Review
- Syndecan receptors: pericellular regulators in development and inflammatory disease.Open biology · 2021Review
- High-speed single-molecule imaging reveals signal transduction by induced transbilayer raft phases.The Journal of cell biology · 2020Article
- Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium.International journal of molecular sciences · 2020Article
- Mapping the Interactome of the Nuclear Heparan Sulfate Proteoglycan Syndecan-1 in Mesothelioma Cells.Biomolecules · 2020Article
- Astaxanthin Prevents Human Papillomavirus L1 Protein Binding in Human Sperm Membranes.Marine drugs · 2018Article
- The heparan sulfate proteoglycan grip on hyperlipidemia and atherosclerosis.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Endocytosis via rafts has attracted considerable recent interest, but the molecular mediators remain incompletely characterized. Here, we focused on the syndecan-1 heparan sulfate proteoglycan, a highly conserved, multifunctional receptor that we previously showed to undergo raft-dependent endocytosis upon clustering. Alanine scanning mutagenesis of three to five consecutive cytoplasmic residues at a time revealed that a conserved juxtamembrane motif, MKKK, was the only region required for efficient endocytosis after clustering. Endocytosis of clustered syndecan-1 occurs in two phases, each requiring a kinase and a corresponding cytoskeletal partner. In the initial phase, ligands trigger rapid MKKK-dependent activation of ERK and the localization of syndecan-1 into rafts. Activation of ERK drives the dissociation of syndecan-1 from α-tubulin, a molecule that may act as an anchor for syndecan-1 at the plasma membrane in the basal state. In the second phase, Src family kinases phosphorylate tyrosyl residues within the transmembrane and cytoplasmic regions of syndecan-1, a process that also requires MKKK. Tyrosine phosphorylation of syndecan-1 triggers the robust recruitment of cortactin, which we found to be an essential mediator of efficient actin-dependent endocytosis. These findings represent the first detailed characterization of the molecular events that drive endocytosis of a raft-dependent receptor and identify a novel endocytic motif, MKKK. Moreover, the results provide new tools to study syndecan function and regulation during uptake of its biologically and medically important ligands, such as HIV-1, atherogenic postprandial remnant lipoproteins, and molecules implicated in Alzheimer disease.
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