Extracellular vesicles released by keratinocytes regulate melanosome maturation, melanocyte dendricity, and pigment transfer

• 成果类型: Article
• 署名作者: Prosperi, Marie- Therese; Giordano, Cecile; Gomez-Duro, Mireia; Hurbain, Ilse; Mace, Anne- Sophie; Raposo, Graca; D'Angelo, Gisela
• 署名单位: Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9127
• DOI: 10.1073/pnas.2321323121
• 发表日期: 2024-04-16
• 关键词: LOCALIZATION; exosomes; protein; light; rac1; rho

摘要

Extracellular vesicles (EVs) facilitate the transfer of proteins, lipids, and genetic material between cells and are recognized as an additional mechanism for sustaining intercellular communication. In the epidermis, the communication between melanocytes and keratinocytes is tightly regulated to warrant skin pigmentation. Melanocytes synthesize the melanin pigment in melanosomes that are transported along the dendrites prior to the transfer of melanin pigment to keratinocytes. EVs secreted by keratinocytes modulate pigmentation in melanocytes [(A. Lo Cicero et al., Nat. Commun. 6, 7506 (2015)]. However, whether EVs secreted by keratinocytes contribute to additional processes essential for melanocyte functions remains elusive. Here, we show that keratinocyte EVs enhance the ability of melanocytes to generate dendrites and mature melanosomes and promote their efficient transfer. Further, keratinocyte EVs carrying Rac1 induce important morphological changes, promote dendrite outgrowth, and potentiate melanin transfer to keratinocytes. Hence, in addition to modulating pigmentation, keratinocytes exploit EVs to control melanocyte plasticity and transfer capacity. These data demonstrate that keratinocyte- derived EVs, by regulating melanocyte functions, are major contributors to cutaneous pigmentation and expand our understanding of the mechanism underlying skin pigmentation via a paracrine EV- mediated communication.