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Updated: Jun 28, 2026

Single-Molecule Localization Microscopy of Membrane Proteins using Single-Antibody Labeling
Published on: March 20, 2026
Trafficking and function of the tetraspanin CD63
Maaike S Pols1, Judith Klumperman
1Cell Microscopy Center, Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands.
Tetraspanin CD63, found in cell surface microdomains and endosomes, is crucial for cellular processes. This review explores CD63 trafficking, its role in exosome secretion, and its involvement in cancer progression.
Area of Science:
- Cell Biology
- Molecular Medicine
- Cancer Research
Background:
- Tetraspanins are cell surface proteins involved in cellular processes.
- Tetraspanin-enriched microdomains (TEMs) are networks of proteins at the cell surface.
- CD63 is a well-characterized tetraspanin with diverse cellular localizations.
Purpose of the Study:
- To review current understanding of CD63 intracellular trafficking.
- To highlight CD63's emerging role as a transport regulator.
- To discuss the implications of CD63 in cancer.
Main Methods:
- Literature review of studies on CD63 localization and trafficking.
- Analysis of CD63's role in endocytosis pathways, including clathrin-dependent and caveolae-mediated routes.
- Examination of CD63's function in exosome biogenesis and secretion.
Main Results:
- CD63 exhibits complex localization, present in TEMs, late endosomes, and lysosomes.
- Evidence supports a role for caveolae in CD63 endocytosis, alongside clathrin.
- CD63 is enriched in intraluminal vesicles of late endosomes, contributing to exosome formation.
Conclusions:
- CD63 intracellular trafficking is tightly regulated, influencing its function.
- CD63 acts as a transport regulator for its interaction partners.
- Dysregulation of CD63 is implicated in cancer development and progression.
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