Melanin processing by keratinocytes: A non‐microbial type of host‐pathogen interaction?. (15th March 2019)

• Record Type: Journal Article
• Authors: Moreiras, Hugo; Lopes‐da‐Silva, Mafalda; Seabra, Miguel C.; Barral, Duarte C.
• Is Part Of: Traffic. Volume 20:Number 4(2019)
• Page Start: 301
• Page End: 304
• Publication Date: 2019-03-15
• Subjects: autophagy -- endocytic pathway -- melanin -- membrane traffic -- Plasmodium -- UV‐radiation; Biological transport -- Periodicals; 571.6
• DOI: 10.1111/tra.12638
• Languages: English
• ISSNs: 1398-9219

Abstract

Abstract : The mechanisms that regulate skin pigmentation have been the subject of intense research in recent decades. In contrast with melanin biogenesis and transport within melanocytes, little is known about how melanin is transferred and processed within keratinocytes. Several models have been proposed for how melanin is transferred, with strong evidence supporting coupled exo/endocytosis. Recently, two reports suggest that upon internalization, melanin is stored within keratinocytes in an arrested compartment, allowing the pigment to persist for long periods. In this commentary, we identify a striking parallelism between melanin processing within keratinocytes and the host‐pathogen interaction with Plasmodium, opening new avenues to understand the complex molecular mechanisms that ensure skin pigmentation and photoprotection. Abstract : Schematic representation of the similarities between melanin processing within keratinocytes and host‐pathogen interaction between hepatocytes and Plasmodium during liver stage infection. Upon internalization by keratinocytes in a PAR‐2‐dependent‐manner, melanocores are processed and acquire first early endocytic markers (EEA1 and Rab5) and then late endocytic markers (LAMP1/2 and CD63), residing in a compartment that is not highly acidic or highly degradative and polarising to the supranuclear region, where melanin protects nuclear DNA from ultraviolet (UV)‐radiation. We speculate that at this stage, compartments containing harmful UV‐modified melanin acquire autophagic markers like LC3‐II to target it for degradation. In hepatocytes, upon Plasmodium internalization the parasite subverts the late endocytic pathway of the host cell to grow in a hybrid compartment that is positive for late endocytic (LAMP1/2, CD63 and Rab7) and autophagic markers (LC3) but is not able to become highly acidic, allowing the parasite to grow and fulfil its life cycle during the liver stage of infection.