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

Guillaume van Niel1, Stéphanie Charrin, Sabrina Simoes

  • 1Institut Curie, Centre de Recherche, F-75248 Paris, France. guillaume.van-niel@curie.fr

Developmental Cell
|October 4, 2011
PubMed

Insights

The tetraspanin CD63 protein is crucial for sorting the PMEL protein into intraluminal vesicles (ILVs) during melanosome biogenesis. CD63 regulates this process independently of ESCRT, impacting amyloid formation and organelle development.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Lysosome-related organelle (LRO) biogenesis relies on cargo sorting into intraluminal vesicles (ILVs) within multivesicular endosomes.
  • The protein PMEL is essential for melanocyte LROs (melanosomes) and undergoes ESCRT-independent sorting to ILVs for amyloid fibril assembly.

Purpose of the Study:

  • To investigate the role of the tetraspanin CD63 in the ESCRT-independent sorting of PMEL to ILVs.
  • To elucidate the interplay between CD63 and ESCRT pathways in cargo sorting during LRO biogenesis.

Main Methods:

  • Utilized cell culture and mouse models to inactivate CD63.
  • Analyzed PMEL sorting, amyloidogenesis, and melanosome morphogenesis.
  • Investigated the fate of PMEL luminal and transmembrane fragments.

Main Results:

  • CD63 directly mediates the ESCRT-independent sorting of the PMEL luminal domain to ILVs.
  • CD63 inactivation impairs PMEL amyloidogenesis and melanosome morphogenesis.
  • Disposal of the PMEL transmembrane fragment requires ESCRTs, and in CD63's absence, the luminal domain is also degraded via the ESCRT pathway.

Conclusions:

  • CD63 plays a direct role in the ESCRT-independent sorting of PMEL luminal domain to ILVs.
  • A coordinated mechanism exists where CD63 regulates one sorting pathway, while ESCRTs handle another for different parts of the same cargo.
  • This highlights a complex interplay between CD63 and ESCRT-dependent processes in cargo sorting critical for LRO biogenesis.

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