Melanin synthesis in the human skin epidermis occurs within melanocyte-specific organelles called melanosomes, which are transferred when mature to adjacent keratinocytes of the basal layer (S. basale). There they undergo additional processing and redistribution to form supra-nuclear melanin caps, which protect the genetic material of these highly proliferative keratinocytes from ultraviolet radiation (UVR)-induced damage. Sharing of organelles between two different cell types like this, is highly unusual in mammalian biology; perhaps reflecting that observation that our species was ‘born’ under the sun. There remains however, a very considerable clinical unmet need for dealing with hypopigmentary/ hyperpigmentary conditions (e.g., vitiligo, melasma, solar lentigines etc.), which exert significant clinical and personal burdens.
If I had a euro for every study that crosses my desk that purports to describe a new human skin pigmentation wonder modulator, I would now be a rich man. Moreover, the surfeit of pigment modulator data based on the ubiquitous mouse dermal melanoma-derived B16 cell lines, and other cell lines turned feral by either nature's or the researcher's hand, can make it difficult to progress pigmentation research that is relevant to human skin.
Much is known about melanogenesis in human melanocytes and a moderate is known amount about how melanin is transferred from melanocytes to keratinocytes. However, we know little about the fate of melanin once inside keratinocytes; where the optical properties of skin pigmentation are largely perceived. We recently reported that melanin fate in progenitor keratinocytes is regulated by a most unusual and rare asymmetric organelle distribution/movement during keratinocyte division. Here, the daughter cell destined to remain in the S. basale ‘inherits’ the preponderance of the melanin cargo of the dividing mother keratinocyte, with the stratifying daughter keratinocyte entering the mid and upper epidermis with only a few melanin granules. Subsequently, we explored using short-term ex vivo cultures of human skin explants, the role of the melanin-laden keratinocyte’s cytoskeleton (i.e., actin, microtubules, and centrosome-associated machinery) in re-distributing melanin within keratinocytes. We conclude that once melanin granules are transferred to keratinocytes, their preferred final apical destination (i.e., to form melanin caps) appears to be facilitated by the coordinated movement of centrosomes and centriolar satellites. In this way, this mechanism may contribute to controlling melanin’s strategic position within UVR-exposed KCs.