Melanin Transferred to Keratinocytes Resides in Nondegradative Endocytic Compartments

Abstract

Melanin transfer from melanocytes to keratinocytes and subsequent accumulation in the supranuclear region is a critical process in skin pigmentation and protection against UVR. We have previously proposed that the main mode of transfer between melanocytes and keratinocytes is through exo/endocytosis of the melanosome core, termed melanocore. In this study, we developed an in vitro uptake assay using melanocores secreted by melanocytes. We show that the uptake of melanocores, but not melanosomes, by keratinocytes is protease-activated receptor-2-dependent. Furthermore, we found that the silencing of the early endocytic regulator Rab5b, but not the late endocytic regulators Rab7a or Rab9a, significantly impairs melanocore uptake by keratinocytes. After uptake, we observed that melanin accumulates in compartments that are positive for both early and late endocytic markers. We found that melanin does not localize to either highly degradative or acidic organelles, as assessed by LysoTracker and DQ-BSA staining, despite the abundance of these types of organelles within keratinocytes. Therefore, we propose that melanocore uptake leads to storage of melanin within keratinocytes in hybrid endocytic compartments that are not highly acidic or degradative. By avoiding lysosomal degradation, these specialized endosomes may allow melanin to persist within keratinocytes for long periods.

Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes

“…A group of recent studies indicated that melanocores incorporated in keratinocytes are stored in organelles expressing lysosomal membrane proteins but lacking a membrane structure (Correia et al, ; Hurbain et al, ). Therefore, we examined PHEKs containing isolated melanosomes and also PHEKs containing isolated melanocores to determine whether PTPD‐12 could decrease the melanin content in those cells.…”

“…Moreover, previous studies only showed steady‐state melanosomes that were readily transferred to keratinocytes, which might not reflect the range of dynamic intercellular communications that occur during melanosome uptake. The main mode of melanin transfer from melanocytes to keratinocytes is exo/endocytosis of the melanosome core, termed melanocore, which leads to the storage of melanin in endocytic compartments that are not highly acidic nor degradative (Correia et al, ). Therefore, we evaluated the effect of PTPD‐12 on melanin content in isolated melanosome‐laden keratinocytes as well as in melanocore‐containing keratinocytes.…”

Oxidative Modifications of Parkin Underlie its Selective Neuroprotection in Adult Human Brain

“…4i,j), our results have not yet revealed the fate of oxidized parkin in other neurons. Human LAMP proteins have been shown to store melanin in human keratinocytes to protect them from UV light 22 . Thus, oxidized parkin together with LAMP-3 (and possibly, LAMP-2) could play a similar role in the ongoing storage of neuromelanin and other radicals, thus facilitating their effective sequestration in ageing brain.…”

“…4i). Of note, LAMP homologues have been shown to promote long term storage of melanin in human keratinocytes 22 ; moreover, variants at the LAMP-3 locus have recently been linked to PD susceptibility 23 .…”

Study of hyperpigmentation in human skin disorder using different electron microscopy techniques

“…To show if the melanin moves itself without membrane, electron tomography was used to obtain a better resolution. Recently, Correia et al (, in press) reported that the uptake of melanocores, but not melanosomes, by keratinocytes is protease‐activated receptor (PAR)‐2‐dependent. In addition, the endocytic regulators Rab5b, Rab7a, and Rab9a were reported as significant factors for melanocore uptake by keratinocytes (Correia et al, , in press).…”