Routing of the RAB6 secretory pathway towards the lysosome related organelle of melanocytes

Nat Commun. 2017 Jun 13:8:15835. doi: 10.1038/ncomms15835.

Abstract

Exocytic carriers convey neo-synthesized components from the Golgi apparatus to the cell surface. While the release and anterograde movement of Golgi-derived vesicles require the small GTPase RAB6, its effector ELKS promotes the targeting and docking of secretory vesicles to particular areas of the plasma membrane. Here, we show that specialized cell types exploit and divert the secretory pathway towards lysosome related organelles. In cultured melanocytes, the secretory route relies on RAB6 and ELKS to directly transport and dock Golgi-derived carriers to melanosomes. By delivering specific cargos, such as MART-1 and TYRP2/ DCT, the RAB6/ELKS-dependent secretory pathway controls the formation and maturation of melanosomes but also pigment synthesis. In addition, pigmentation defects are observed in RAB6 KO mice. Our data together reveal for the first time that the secretory pathway can be directed towards intracellular organelles of endosomal origin to ensure their biogenesis and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Endosomes / genetics
  • Endosomes / metabolism
  • Female
  • Golgi Apparatus / genetics
  • Golgi Apparatus / metabolism
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Male
  • Melanocytes / metabolism*
  • Melanosomes / genetics
  • Melanosomes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Protein Transport
  • Secretory Pathway
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • Carrier Proteins
  • Erc1 protein, mouse
  • Nerve Tissue Proteins
  • Rab6 protein
  • rab GTP-Binding Proteins