Biogenesis and fate of pigment granules in human skin

 

In the skin epidermis, pigmented melanocytes contact and communicate with neighboring keratinocytes. Within the melanocyte, the pigment melanin is synthesized and stored in an organelle, the melanosome. Later, the pigment is transferred to the keratinocyte in a new organelle that is positioned near the nucleus to protect the genetic material against the harmful effects of UV radiation. Melanosome biogenesis and pigment synthesis, as well as its transfer between cells, or its packaging, maintenance and positioning in keratinocytes are processes dependent on the membrane dynamics and trafficking. Many of the components involved are mutated or mis-regulated in genetic forms of albinism or skin cancers, such as melanoma. Overall, we decipher how melanocytes and keratinocytes coordinate their intracellular trafficking to orchestrate the skin coloration and protection against solar radiation. Especially, we study :

 

-The membrane dynamics processes during trafficking in and out of melanosomes.

 

-The trafficking components involved and their defects in pigment disorders.

 

-The cell biology of the pigment and its functions in the keratinocyte.

 

Main contributions (last 5 years):

Domingues, L., I. Hurbain, F. Gilles-Marsens, J. Sirés-Campos, N. André, M. Dewulf, M. Romao, C. Viaris de Lesegno, A.-S. Macé, C. Blouin, C. Guéré, K. Vié, G. Raposo, C. Lamaze, and C. Delevoye. 2020. Coupling of melanocyte signaling and mechanics by caveolae is required for human skin pigmentation. Nat. Commun. 11:2988. doi:10.1038/s41467-020-16738-z.

Delevoye, C., M.S. Marks, and G. Raposo. 2019. Lysosome-related organelles as functional adaptations of the endolysosomal system. Curr. Opin. Cell Biol. 59:147–158. doi:10.1016/j.ceb.2019.05.003.

Bissig, C., P. Croisé, X. Heiligenstein, I. Hurbain, G.M. Lenk, E. Kaufman, R. Sannerud, W. Annaert, M.H. Meisler, L.S. Weisman, G. Raposo, and G. van Niel. 2019. PIKfyve complex regulates early melanosome homeostasis required for physiological amyloid formation. J. Cell Sci. doi:10.1242/jcs.229500.

Ripoll, L., X. Heiligenstein, I. Hurbain, L. Domingues, F. Figon, K.J. Petersen, M.K. Dennis, A. Houdusse, M.S. Marks, G. Raposo, and C. Delevoye. 2018. Myosin VI and branched actin filaments mediate membrane constriction and fission of melanosomal tubule carriers. J. Cell Biol. doi:10.1083/jcb.201709055.

Campagne, C., L. Ripoll, F. Gilles-Marsens, G. Raposo, and C. Delevoye. 2018. AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis. Int. J. Mol. Sci. 19. doi:10.3390/ijms19020568.

Hurbain, I., M. Romao, P. Sextius, E. Bourreau, C. Marchal, F. Bernerd, C. Duval, and G. Raposo. 2017. Melanosome distribution in keratinocytes in different skin types: melanosome clusters are not degradative organelles. J. Invest. Dermatol. doi:10.1016/j.jid.2017.09.039.

Patwardhan, A., S. Bardin, S. Miserey-Lenkei, L. Larue, B. Goud, G. Raposo, and C. Delevoye. 2017. Routing of the RAB6 secretory pathway towards the lysosome related organelle of melanocytes. Nat. Commun. 8:15835. doi:10.1038/ncomms15835.

Delevoye, C., X. Heiligenstein, L. Ripoll, F. Gilles-Marsens, M.K. Dennis, R.A. Linares, L. Derman, A. Gokhale, E. Morel, V. Faundez, M.S. Marks, and G. Raposo. 2016. BLOC-1 Brings Together the Actin and Microtubule Cytoskeletons to Generate Recycling Endosomes. Curr. Biol. CB. 26:1–13. doi:10.1016/j.cub.2015.11.020.