Melanin Transferred to Keratinocytes Resides in Nondegradative Endocytic Compartments

Melanocores within keratinocytes are surrounded by a single membrane lacking the melanosome marker TYRP1, implying the original melanosome membrane is lost during transfer.

“We also showed that melanocores within keratinocytes are surrounded by a single membrane lacking the melanosome marker TYRP1, implying that the original melanosome membrane is lost during transfer [ 19 , 27 ].”

The way melanin is presented to keratinocytes (naked melanin in melanocores or membrane-bound melanosomes) results in activation of different receptors and possibly distinct downstream signaling pathways.

“Therefore, these reports reinforce the notion that the way melanin is presented to keratinocytes, i.e., naked melanin in melanocores or membrane-bound melanosomes, results in the activation of different receptors and possibly distinct downstream signaling pathways [ 27 , 49 , 50 ].”

Although melanin is long-lived inside keratinocytes in vitro, it localizes mostly to the basal layer, and its accumulation throughout the epidermis is only evident in darker phototypes, where suprabasal keratinocytes retain degraded melanin fragments known as "melanin dust".

“Although melanin is long-lived inside keratinocytes in vitro, it localizes mostly to the basal layer, and its accumulation throughout the epidermis is only evident in darker phototypes, where suprabasal keratinocytes retain degraded melanin fragments known as “melanin dust”.”

Melanin accumulates in moderately acidic compartments with low degradative capacity, as shown by low Lysotracker and DAMP accumulation and low DQ-BSA fluorescence, despite the abundance of these organelles within keratinocytes.

“Moreover, we and Graça Raposo’s group showed that melanin accumulates in moderately acidic compartments (presenting low levels of Lysotracker and DAMP [3-(2,4-dinitroanilino)-3′-amino-N-methyldipropylamine] accumulation) with low degradative capacity, as shown by the low levels of dye quenched-bovine serum albumin (DQ-BSA) fluorescence, despite the abundance of these types of organelles within ker”

MKSs are likely unique melanin-storage compartments presenting low acidity and degradative capacity but maintaining characteristics of LEs/lysosomes, including membrane markers LAMP1/2 and CD63.

“MKSs are likely unique melanin-storage compartments presenting low acidity and degradative capacity but maintaining characteristics of LEs/lysosomes, including the membrane markers LAMP1/2 and CD63 [ 18 , 27 ]”

Melanocores but not melanosomes are dependent on PAR-2 for their uptake by keratinocytes.

“Furthermore, our group showed that melanocores but not melanosomes are dependent on PAR-2 for their uptake by keratinocytes, supporting the idea that melanocores are the form of melanin transferred to keratinocytes and the model of exo-/phagocytosis [ 27 , 49 ] ( Figure 3 B).”

The finding that melanocores but not melanosomes depend on PAR-2 supports the idea that melanocores are the form of melanin transferred to keratinocytes and the exo-/phagocytosis model.

“supporting the idea that melanocores are the form of melanin transferred to keratinocytes and the model of exo-/phagocytosis [ 27 , 49 ]”

In mouse keratinocytes, melanin-containing compartments are positive for EEA1 and Rab5, as well as for LAMP2 and CD63.

“Additionally, we found that in mouse keratinocytes, melanin-containing compartments are positive for the early endocytic markers early endosome antigen 1 (EEA1) and Rab5, as well as for LAMP2 and CD63 [ 27 ]”

In cultured mouse keratinocytes, melanin is long-lived and persists for long periods.

“Indeed, we reported that in cultured mouse keratinocytes, melanin is long-lived and persists for long periods [ 27 ]”

TLR-3 can regulate melanocore and melanosome internalization by keratinocytes.

“others showed that TLR-3 can regulate melanocore and melanosome internalization by keratinocytes [ 27 , 49 , 50 ].”

Detection of melanin in the corneal layer ("melanin dust"), observed when using Fontana Masson staining, can hardly be found by EM and is therefore attributed to an artifact of this staining.

“Of note, the detection of melanin in the corneal layer ( “melanin dust”), observed when using Fontana Masson staining, can hardly be found by EM and is therefore attributed to an artifact of this staining [ 27 , 82 , 92 , 115 , 116 ].”