Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

Abstract

Melanin granules cluster within supra-nuclear caps in basal keratinocytes (KCs) of the human epidermis, where they protect KC genomic DNA against ultraviolet radiation (UVR) damage. While much is known about melanogenesis in melanocytes (MCs) and a moderate amount about melanin transfer from MC to KC, we know little about the fate of melanin once inside KCs. We recently reported that melanin fate in progenitor KCs is regulated by rare asymmetric organelle movement during mitosis. Here, we explore the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. Short-term cultures of human skin explants were treated with cytochalasin-B and nocodazole to target actin filaments and microtubules, respectively. Treatment effects on melanin distribution were assessed by the Warthin–Starry stain, on centrosome-associated proteins by immunofluorescence microscopy, and on co-localisation with melanin granules by brightfield microscopy. Cytochalasin-B treatment disassembled supra-nuclear melanin caps, while nocodazole treatment moved melanin from the apical to basal KC domain. Centrosome and centriolar satellite-associated proteins showed a high degree of co-localisation with melanin. Thus, once melanin granules are transferred to KCs, their preferred apical distribution appears to be facilitated by coordinated movement of centrosomes and centriolar satellites. This mechanism may control melanin’s strategic position within UVR-exposed KCs.

Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms

“…This localization was shown to be dependent on cytoplasmic dynein and dynactin to aggregate melanokerasomes at the perinuclear region [ 74 ]. Also, it was recently shown that the apical distribution of melanin after being transferred to keratinocytes is regulated by the centrosome and centriolar satellites [ 75 ]. Importantly, microtubules and actin cytoskeleton networks seem to maintain melanokerasomes in the apical domain of proliferative keratinocytes, protecting these cells from UVR-induced damage.…”

Successful Repigmentation of Full-Thickness Wound Healing in Fraser’s Dolphins (Lagenodelphis hosei)

“…It has been considered that melanin granules are positioned apically to provide protection against UVR-induced damage [ 3 , 36 ] A recent study showed that cell polarity and the movement of centrosomes and centriolar satellites are implicated in apical distribution of melanin within the human keratinocytes [ 41 ]. The previous study in several cetacean species has described the phenomena that melanin granules were arranged apically within keratinocytes [ 36 ] although the color of analyzed skin samples was not described.…”

Comparative analysis of skin color in breast reconstruction using pedicled transverse rectus abdominis myocutaneous flaps

“…It is likely that the skin in flaps had lower melanocyte function than normal, undamaged skin. One possible explanation relates to the fact that melanocytes are confined to the human epidermis; therefore, when an incision is made for the flap, transient relative ischemia and hypothermia damage melanocytes [9,10]. This may be a reason why the flap melanin levels were observed to be lower than those of abdominal skin.…”