Other news

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

In an article published in Nature Communications, Anand Patwardhan and Cédric Delevoye, from Graça Raposo group (CNRS/Institut Curie) in collaboration with the teams of Bruno Goud (CNRS/Institut Curie) and Lionel Larue (Inserm/Institut Curie), described a novel intracellular route used by melanocyte to direct components required for melanin synthesis to its pigment granule, the melanosome.

Pigmentation in humans is one of the most obvious traits. Besides its cosmetic role, the melanin pigment produced by skin melanocytes provides a natural sunscreen that protects our body against UV solar radiations. Even if pigmentation is vital, how those melanocytes manage to produce, store and keep melanin functional are not totally understood.

Electron micrograph of retinal pigment epithelium from eyes of wild-type (left) and Rab6 KO mice (right). Note the dramatic reduction in the number of pigmented melanosomes (dark round/ ovoid structures) in KO relative to WT.
Electron micrograph of retinal pigment epithelium from eyes of wild-type (left) and Rab6 KO mice (right). Note the dramatic reduction in the number of pigmented melanosomes (dark round/ ovoid structures) in KO relative to WT.

This route starts at the Golgi apparatus and shares features with the well-known secretory pathway by relying on the small GTPase RAB6 and its effector ELKS. However, instead of targeting the plasma membrane, this new “secretory pathway” conveys pigment-related proteins and ends up to the melanosome. This represents the first example of a diversion of the secretory pathway towards an intracellular organelle. Finally, this alternative route ensures pigmentation in vitro as well as in vivo in mice (see pictures).

Together, this study reveals how specialized cell types can tune and optimize their intracellular trafficking in order to fulfill their unique function. It remains now to investigate whether this novel secretory route may be exploited by other specialized cells, or targeted in pigmentary disorders or skin cancers like melanoma.

Routing of the RAB6 secretory pathway towards the lysosome related organelle of melanocytes
Anand Patwardhan, Sabine Bardin, Stéphanie Miserey-Lenkei, Lionel Larue, Bruno Goud, Graça Raposo & Cédric Delevoye
Nature Communications, doi:10.1038/ncomms15835, 13 June 2017