The tetraspanin CD63 regulates ESCRT-independent and dependent endosomal sorting during melanogenesis

By Guillaume van Niel, Stéphanie Charrin, Sabrina Simoes, M. Romao, Leila Rochin, P. Saftig, M. Marks, E. Rubinstein, G. Raposo. Developmental Cell, 2011

881 citations recorded by the source corpus.

Summary Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for numerous physiological processes including lysosome-related organelle (LRO) biogenesis. PMEL – a component of melanocyte LROs (melanosomes) – is sorted to ILVs in an ESCRT-independent manner, where it is proteolytically processed and assembled into functional amyloid fibrils during melanosome maturation. Here we show that the tetraspanin CD63 directly participates in ESCRT-independent sorting of the PMEL luminal domain, but not of traditional ESCRT-dependent cargoes, to ILVs. Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis. Whereas CD63 is required for normal PMEL luminal domain sorting, the disposal of the remaining PMEL transmembrane fragment requires functional ESCRTs but not CD63. In the absence of CD63, the PMEL luminal domain follows this fragment and is targeted for ESCRT-dependent degradation. Our data thus reveal a tight interplay regulated by CD63 between two distinct endosomal ILV sorting processes for a single cargo during LRO biogenesis.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8ae042e0023811eea8265260dc590e47e0a725c1

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Citations in the corpus

Exosomes as a new frontier of cancer liquid biopsy (2022, background): “The mechanisms of cargo sorting are still unclear, both endosomal sorting complex required for transport (ESCRT)-dependent manner [30, 31] and ESCRT-independent mechanism have been reported to participate in this process [32, 33].”
Extracellular Vesicles: Unique Intercellular Delivery Vehicles. (2017, background): “A third mechanism that has been proposed for exosome biogenesis is tetraspanin-mediated organization of specific proteins, such as the amyloidogenic protein, premelanosome protein (PMEL) [33,34].”
Exosomes in cancer development, metastasis, and immunity (2019, background): “[PubMed: 21570275] [24]. van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G, The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis, Dev Cell, 21 (2011) 708–721, DOI: 10.1016/j.devcel.2011.08.019.”
Engineering exosomes for targeted drug delivery (2021, background): “For example, CD63 sorts melanoma-related proteins into human ILVs in the absence of ESCRT and ceramide [27].”
Cells release subpopulations of exosomes with distinct molecular and biological properties (2016, neutral): “‘Vesicle mediated transport’, ‘translation’, ‘cytoskeleton’, ‘G-protein’, ‘ribosomal protein’, ‘small GTPase’ and ‘chaperones’, were commonly enriched terms, a finding which is in line with our previous observations on exosome content (15, 17).”
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Challenges and directions in studying cell–cell communication by extracellular vesicles (2022, background): “EVs can be directly released into biological fluids (8) or reach them by transcytosis or by passing through breaches of biological barriers (9) to disseminate through the organism via the circulation (10).”
Tetraspanins in Extracellular Vesicle Formation and Function (2014, background): “In this ESCRT-independent pathway, tetraspanins seem to play a fundamental role (73, 75).”
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Biogenesis and secretion of exosomes. (2014, neutral): “In human melanoma cells, CD63 allows sorting of a melanosomal protein into ILVs, in a ceramide-and ESCRT-independent manner [51].”