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Heparan sulfate proteoglycan as a cell-surface endocytosis receptor
Open accessAbstract
How various macromolecules are exchanged between cells and how they gain entry into recipient cells are fundamental questions in cell biology with important implications e.g. non-viral drug delivery, infectious disease, metabolic disorders, and cancer. The role of heparan sulfate proteoglycan (HSPG) as a cell-surface receptor of diverse macromolecular cargo has recently been manifested. Exosomes, cell penetrating peptides, polycation–nucleic acid complexes, viruses, lipoproteins, growth factors and morphogens among other ligands enter cells through HSPG-mediated endocytosis. Key questions that partially have been unraveled over recent years include the respective roles of HSPG core protein and HS chain structure specificity for macromolecular cargo endocytosis, the down-stream intracellular signaling events involved in HSPG-dependent membrane invagination and vesicle formation, and the biological significance of the HSPG transport pathway. Here, we discuss the intriguing role of HSPGs as a major entry pathway of macromolecules in mammalian cells with emphasis on recent in vitro and in vivo data that provide compelling evidence of HSPG as an autonomous endocytosis receptor. • Heparan sulfate proteoglycan (HSPG) is a receptor of diverse macromolecular cargo. • HSPG endocytosis is involved in infectious disease, lipid metabolism and cancer. • HSPG represents an interesting target for macromolecular drug delivery. • Recent findings on the intriguing role of HSPG-mediated transport are discussed.
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“However, HSPGs are known to act both independently and in concert with co-receptors to mediate endocytosis26.”
From LRP1 is a master regulator of tau uptake and spread (2020) · cites this paper as [26]
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“Meanwhile, the extracellular tau can be taken up by neighboring cells, both neurons and glial cells, through various pathways, including phagocytosis [68], macropinocytosis [69], receptor-mediated uptake [67, 70], endocytosis [71], and/or membrane fusion of exosomes [72, 73].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [71]
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Metadata
- Authors
- Christianson, H. C., & Belting, M.
- Affiliations
- Lund University (SE)
- Corresponding author
- Belting, Mattias
- ORCID
- Belting, Mattias
- Venue
- Matrix Biology
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 35
- Pages
- 51-55
- ISSN
- 0945-053X (ISSN-L)
- OpenAlex
- W1980226233
- Cited by
- 429
- References
- 55
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 29 · 2023: 44 · 2022: 43 · 2021: 44 · 2020: 54 · 2019: 37 · 2018: 27 · 2017: 29 · 2016: 30 · 2015: 28 · 2014: 14
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Matrix Biology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Cancer Fund
- Swedish Research Council
- Gunnar Nilsson Cancer Foundation
- Anna Lisa and Sven Eric Lundgren Foundation
- Kamprad Family Foundation
- Skåne University Hospital
- Governmental funding of clinical research within the national health services (ALF)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- heparan sulfate proteoglycans, endocytosis, cell surface receptors, exosomes, cell-penetrating peptides, nucleic acid delivery, viral entry, lipoprotein uptake, growth factor signaling, membrane invagination, intracellular signaling, lipid metabolism, cancer, infectious diseases, drug delivery
- MeSH terms
- Animals, Biological Transport, Endocytosis, Humans, Ligands, Models, Biological, Receptors, Cell Surface, Signal Transduction, Heparan Sulfate Proteoglycans
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