Trafficking and function of the tetraspanin CD63
Abstract
Tetraspanins comprise a large superfamily of cell surface-associated membrane proteins characterized by four transmembrane domains. They participate in a variety of cellular processes, like cell activation, adhesion, differentiation and tumour invasion. At the cell surface, tetraspanins form networks with a wide diversity of proteins called tetraspanin-enriched microdomains (TEMs). CD63 was the first characterized tetraspanin. In addition to its presence in TEMs, CD63 is also abundantly present in late endosomes and lysosomes. CD63 at the cell surface is endocytosed via a clathrin-dependent pathway, although recent studies suggest the involvement of other pathways as well and we here present evidence for a role of caveolae in CD63 endocytosis. In late endosomes, CD63 is enriched on the intraluminal vesicles, which by specialized cells are secreted as exosomes through fusion of endosomes with the plasma membrane. The complex localization pattern of CD63 suggests that its intracellular trafficking and distribution must be tightly regulated. In this review we discuss the latest insights in CD63 trafficking and its emerging function as a transport regulator of its interaction partners. Finally, the involvement of CD63 in cancer will be discussed.
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CD63 is a ubiquitously expressed protein and the major pool of CD63 resides in late endosomes and lysosomes.
“CD63 is well known as a ubiquitously expressed protein and the major pool of CD63 resides in late endosomes and lysosomes [33,34].”
From Ferroptosis-dependent extracellular vesicles from macrophage contribute to asbestos-induced mesothelial carcinogenesis through loading ferritin (2021) · cites this paper as [34]
ILV formation requires two distinct processes: organization of the endosome membrane into tetraspanin-enriched microdomains (TEMs) and ESCRT complexes.
“Work in yeast [28-31] and other tissue culture models [32-34] suggests that ILV formation requires two distinct processes. The first involves the organization of the endosome membrane into specialized units highly enriched for a class of membrane proteins called tetraspanins [35].”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [35]
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- Authors
- Pols, M. S., & Klumperman, J.
- Affiliations
- University Medical Center Utrecht (NL)
- Corresponding author
- Klumperman, Judith
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 315
- Issue
- 9
- Pages
- 1584-1592
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2057332675
- Cited by
- 745
- References
- 4
- Citations by year
- 2026: 40 · 2025: 63 · 2024: 63 · 2023: 61 · 2022: 52 · 2021: 71 · 2020: 68 · 2019: 48 · 2018: 45 · 2017: 27 · 2016: 47 · 2015: 24 · 2014: 29 · 2013: 26 · 2012: 25
- FWCI
- 1.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- CD63, tetraspanins, tetraspanin-enriched microdomains, endocytosis, caveolae, clathrin-mediated endocytosis, late endosomes, lysosomes, exosomes, intraluminal vesicles, protein trafficking
- MeSH terms
- Animals, Antigen-Presenting Cells, Antigens, Surface, Humans, Membrane Proteins, Neoplasm Proteins, Neoplasms, Neutrophils, Parietal Cells, Gastric, Platelet Membrane Glycoproteins, T-Lymphocytes, Antigens, CD, Protein Transport, Caveolae, Membrane Microdomains, Adaptor Protein Complex 3, Syntenins, Exosomes, Tetraspanin 30
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