Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Melanosome Transport/Transfer and Melanin Pigmentation in the Skin

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Role of Xenobiotics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 49983

Share This Special Issue

Special Issue Editor

Prof. Dr. Hideya Ando

E-Mail Website
Guest Editor

Department of Applied Chemistry and Biotechnology, Okayama University of Science, Okayama, Japan
Interests: melanin; melanocyte; melanosome; pigmentation; tyrosinase; ultraviolet light
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Melanin pigments are produced by melanocytes located in the basal layer of the epidermis and are transferred to keratinocytes. Further, melanin pigments are synthesized only in specialized organelles within melanocytes, termed melanosomes. Those melanosomes move along the cytoskeleton to the dendrites of melanocytes and are delivered to surrounding keratinocytes. Improper melanosome trafficking results in hyper- and hypo-pigmentary disorders such as melasma, age spots, Hermansky-Pudlak/Griscelli syndrome and vitiligo. In addition, in the dermis of post-inflammatory hyperpigmented lesion, the presence of melanophages containing multiple melanosomes are observed occasionally. Many studies have characterized the mechanisms of melanosome transport in melanocytes and melanosome transfer to keratinocytes, but many unknown factors still remain to be clarified. Through the elucidation of these mechanisms, the development of novel remedies for pigmentary disorders is expected. In this Special Issue, reviews and original articles related to melanosome transport/transfer and melanin pigmentation, as well as research topics on the degradation/alteration of melanosomes in the epidermis, are welcome.

Prof. Dr. Hideya Ando
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

endocytosis
exocytosis
fibroblast
keratinocyte
melanin
melanocyte
melanosome
pigmentation
trafficking
transfer

Related Special Issue

Melanosome Transport/Transfer and Melanin Pigmentation in the Skin 2.0 in International Journal of Molecular Sciences (2 articles)

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

12 pages, 2189 KiB

Open AccessArticle

Computational Investigation of the pH Dependence of Stability of Melanosome Proteins: Implication for Melanosome formation and Disease

by Mahesh Koirala, H. B. Mihiri Shashikala, Jacob Jeffries, Bohua Wu, Stacie K. Loftus, Jonathan H. Zippin and Emil Alexov

Int. J. Mol. Sci. 2021, 22(15), 8273; https://doi.org/10.3390/ijms22158273 - 31 Jul 2021

Cited by 2 | Viewed by 2256

Abstract

Intravesicular pH plays a crucial role in melanosome maturation and function. Melanosomal pH changes during maturation from very acidic in the early stages to neutral in late stages. Neutral pH is critical for providing optimal conditions for the rate-limiting, pH-sensitive melanin-synthesizing enzyme tyrosinase (TYR). This dramatic change in pH is thought to result from the activity of several proteins that control melanosomal pH. Here, we computationally investigated the pH-dependent stability of several melanosomal membrane proteins and compared them to the pH dependence of the stability of TYR. We confirmed that the pH optimum of TYR is neutral, and we also found that proteins that are negative regulators of melanosomal pH are predicted to function optimally at neutral pH. In contrast, positive pH regulators were predicted to have an acidic pH optimum. We propose a competitive mechanism among positive and negative regulators that results in pH equilibrium. Our findings are consistent with previous work that demonstrated a correlation between the pH optima of stability and activity, and they are consistent with the expected activity of positive and negative regulators of melanosomal pH. Furthermore, our data suggest that disease-causing variants impact the pH dependence of melanosomal proteins; this is particularly prominent for the OCA2 protein. In conclusion, melanosomal pH appears to affect the activity of multiple melanosomal proteins. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Graphical abstract

16 pages, 1707 KiB

Open AccessCommunication

Novel Chemically Modified Curcumin (CMC) Analogs Exhibit Anti-Melanogenic Activity in Primary Human Melanocytes

by Shilpi Goenka and Sanford R. Simon

Int. J. Mol. Sci. 2021, 22(11), 6043; https://doi.org/10.3390/ijms22116043 - 03 Jun 2021

Cited by 11 | Viewed by 2867

Abstract

Hyperpigmentation is a dermatological condition characterized by the overaccumulation and/or oversecretion of melanin pigment. The efficacy of curcumin as an anti-melanogenic therapeutic has been recognized, but the poor stability and solubility that have limited its use have inspired the synthesis of novel curcumin analogs. We have previously reported on comparisons of the anti-melanogenic activity of four novel chemically modified curcumin (CMC) analogs, CMC2.14, CMC2.5, CMC2.23 and CMC2.24, with that of parent curcumin (PC), using a B16F10 mouse melanoma cell model, and we have investigated mechanisms of inhibition. In the current study, we have extended our findings using normal human melanocytes from a darkly pigmented donor (HEMn-DP) and we have begun to study aspects of melanosome export to human keratinocytes. Our results showed that all the CMCs downregulated the protein levels of melanogenic paracrine mediators, endothelin-1 (ET-1) and adrenomedullin (ADM) in HaCaT cells and suppressed the phagocytosis of FluoSphere beads that are considered to be melanosome mimics. All the three CMCs were similarly potent (except CMC2.14, which was highly cytotoxic) in inhibiting melanin production; furthermore, they suppressed dendricity in HEMn-DP cells. CMC2.24 and CMC2.23 robustly suppressed cellular tyrosinase activity but did not alter tyrosinase protein levels, while CMC2.5 did not suppress tyrosinase activity but significantly downregulated tyrosinase protein levels, indicative of a distinctive mode of action for the two structurally related CMCs. Moreover, HEMn-DP cells treated with CMC2.24 or CMC2.23 partially recovered their suppressed tyrosinase activity after cessation of the treatment. All the three CMCs were nontoxic to human dermal fibroblasts while PC was highly cytotoxic. Our results provide a proof-of-principle for the novel use of the CMCs for skin depigmentation, since at low concentrations, ranging from 5 to 25 µM, the CMCs (CMC2.24, CMC2.23 and CMC2.5) were more potent anti-melanogenic agents than PC and tetrahydrocurcumin (THC), both of which were ineffective at melanogenesis at similar doses, as tested in HEMn-DP cells (with PC being highly toxic in dermal fibroblasts and keratinocytes). Further studies to evaluate the efficacy of CMCs in human skin tissue and in vivo studies are warranted. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Figure 1

16 pages, 3596 KiB

Open AccessArticle

Marliolide Derivative Induces Melanosome Degradation via Nrf2/p62-Mediated Autophagy

by Cheong-Yong Yun, Nahyun Choi, Jae Un Lee, Eun Jung Lee, Ji Young Kim, Won Jun Choi, Sang Ho Oh and Jong-Hyuk Sung

Int. J. Mol. Sci. 2021, 22(8), 3995; https://doi.org/10.3390/ijms22083995 - 13 Apr 2021

Cited by 10 | Viewed by 3509

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2), which is linked to autophagy regulation and melanogenesis regulation, is activated by marliolide. In this study, we investigated the effect of a marliolide derivative on melanosome degradation through the autophagy pathway. The effect of the marliolide derivative on melanosome degradation was investigated in α-melanocyte stimulating hormone (α-MSH)-treated melanocytes, melanosome-incorporated keratinocyte, and ultraviolet (UV)B-exposed HRM-2 mice (melanin-possessing hairless mice). The marliolide derivative, 5-methyl-3-tetradecylidene-dihydro-furan-2-one (DMF02), decreased melanin pigmentation by melanosome degradation in α-MSH-treated melanocytes and melanosome-incorporated keratinocytes, evidenced by premelanosome protein (PMEL) expression, but did not affect melanogenesis-associated proteins. The UVB-induced hyperpigmentation in HRM-2 mice was also reduced by a topical application of DMF02. DMF02 activated Nrf2 and induced autophagy in vivo, evidenced by decreased PMEL in microtubule-associated proteins 1A/1B light chain 3B (LC3)-II-expressed areas. DMF02 also induced melanosome degradation via autophagy in vitro, and DMF02-induced melanosome degradation was recovered by chloroquine (CQ), which is a lysosomal inhibitor. In addition, Nrf2 silencing by siRNA attenuated the DMF02-induced melanosome degradation via the suppression of p62. DMF02 induced melanosome degradation in melanocytes and keratinocytes by regulating autophagy via Nrf2-p62 activation. Therefore, Nrf2 activator could be a promising therapeutic agent for reducing hyperpigmentation. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Figure 1

19 pages, 5498 KiB

Open AccessArticle

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

by Irene Castellano-Pellicena, Ciaran G. Morrison, Mike Bell, Clare O’Connor and Desmond J. Tobin

Int. J. Mol. Sci. 2021, 22(6), 3143; https://doi.org/10.3390/ijms22063143 - 19 Mar 2021

Cited by 17 | Viewed by 4848

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. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Figure 1

14 pages, 4792 KiB

Open AccessArticle

A Novel Method for Visualizing Melanosome and Melanin Distribution in Human Skin Tissues

by Chikako Yoshikawa-Murakami, Yuki Mizutani, Akemi Ryu, Eiji Naru, Takashi Teramura, Yuta Homma and Mitsunori Fukuda

Int. J. Mol. Sci. 2020, 21(22), 8514; https://doi.org/10.3390/ijms21228514 - 12 Nov 2020

Cited by 2 | Viewed by 4463

Abstract

Melanin incorporated into keratinocytes plays an important role in photoprotection; however, abnormal melanin accumulation causes hyperpigmentary disorders. To understand the mechanism behind the accumulation of excess melanin in the skin, it is essential to clarify the spatial distribution of melanosomes or melanin in the epidermis. Although several markers have been used to detect melanosomes or melanin, no suitable markers to determine the precise localization of melanin in the epidermis have been reported. In this study, we showed that melanocore-interacting Kif1c-tail (M-INK), a recently developed fluorescent probe for visualizing mature melanosomes, binds to purified melanin in vitro, and applied it for detecting melanin in human skin tissues. Frozen skin sections from different phototypes were co-stained for the hemagglutinin (HA)-tagged M-INK probe and markers of melanocytes or keratinocytes, and a wide distribution of melanin was observed in the epidermis. Analysis of the different skin phototypes indicated that the fluorescent signals of HA-M-INK correlated well with skin color. The reconstruction of three-dimensional images of epidermal sheets enabled us to observe the spatial distribution of melanin in the epidermis. Thus, the HA-M-INK probe is an ideal tool to individually visualize melanin (or melanosome) distribution in melanocytes and in keratinocytes in skin tissues. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Figure 1

14 pages, 3436 KiB

Open AccessArticle

Dermal Fibroblasts Internalize Phosphatidylserine-Exposed Secretory Melanosome Clusters and Apoptotic Melanocytes

by Hideya Ando, Satoshi Yoshimoto, Moemi Yoshida, Nene Shimoda, Ryosuke Tadokoro, Haruka Kohda, Mami Ishikawa, Takahito Nishikata, Bunpei Katayama, Toshiyuki Ozawa, Daisuke Tsuruta, Ken-ichi Mizutani, Masayuki Yagi and Masamitsu Ichihashi

Int. J. Mol. Sci. 2020, 21(16), 5789; https://doi.org/10.3390/ijms21165789 - 12 Aug 2020

Cited by 10 | Viewed by 4549

Abstract

Pigmentation in the dermis is known to be caused by melanophages, defined as melanosome-laden macrophages. In this study, we show that dermal fibroblasts also have an ability to uptake melanosomes and apoptotic melanocytes. We have previously demonstrated that normal human melanocytes constantly secrete melanosome clusters from various sites of their dendrites. After adding secreted melanosome clusters collected from the culture medium of melanocytes, time-lapse imaging showed that fibroblasts actively attached to the secreted melanosome clusters and incorporated them. Annexin V staining revealed that phosphatidylserine (PtdSer), which is known as an ‘eat-me’ signal that triggers the internalization of apoptotic cells by macrophages, is exposed on the surface of secreted melanosome clusters. Dermal fibroblasts were able to uptake secreted melanosome clusters as did macrophages, and those fibroblasts express TIM4, a receptor for PtdSer-mediated endocytosis. Further, co-cultures of fibroblasts and melanocytes demonstrated that dermal fibroblasts internalize PtdSer-exposed apoptotic melanocytes. These results suggest that not only macrophages, but also dermal fibroblasts contribute to the collection of potentially toxic substances in the dermis, such as secreted melanosome clusters and apoptotic melanocytes, that have been occasionally observed to drop down into the dermis from the epidermis. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Figure 1

17 pages, 5854 KiB

Open AccessArticle

Autophagy Declines with Premature Skin Aging resulting in Dynamic Alterations in Skin Pigmentation and Epidermal Differentiation

by Daiki Murase, Ayumi Kusaka-Kikushima, Akira Hachiya, Rachel Fullenkamp, Anita Stepp, Asuka Imai, Mizuki Ueno, Keigo Kawabata, Yoshito Takahashi, Tadashi Hase, Atsushi Ohuchi, Shuhei Nakamura and Tamotsu Yoshimori

Int. J. Mol. Sci. 2020, 21(16), 5708; https://doi.org/10.3390/ijms21165708 - 09 Aug 2020

Cited by 19 | Viewed by 5951

Abstract

Autophagy is a membrane traffic system that provides sustainable degradation of cellular components for homeostasis, and is thus considered to promote health and longevity, though its activity declines with aging. The present findings show deterioration of autophagy in association with premature skin aging. Autophagy flux was successfully determined in skin tissues, which demonstrated significantly decreased autophagy in hyperpigmented skin such as that seen in senile lentigo. Furthermore, an exacerbated decline in autophagy was confirmed in xerotic hyperpigmentation areas, accompanied by severe dehydration and a barrier defect, which showed correlations with skin physiological conditions. The enhancement of autophagy in skin ex vivo ameliorated skin integrity, including pigmentation and epidermal differentiation. The present results indicate that the restoration of autophagy can contribute to improving premature skin aging by various intrinsic and extrinsic factors via the normalization of protein homeostasis. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Figure 1

Review

Jump to: Research

11 pages, 1091 KiB

Open AccessReview

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

by Hugo Moreiras, Miguel C. Seabra and Duarte C. Barral

Int. J. Mol. Sci. 2021, 22(9), 4466; https://doi.org/10.3390/ijms22094466 - 24 Apr 2021

Cited by 54 | Viewed by 12034

Abstract

The mechanisms by which the pigment melanin is transferred from melanocytes and processed within keratinocytes to achieve skin pigmentation remain ill-characterized. Nevertheless, several models have emerged in the past decades to explain the transfer process. Here, we review the proposed models for melanin transfer in the skin epidermis, the available evidence supporting each one, and the recent observations in favor of the exo/phagocytosis and shed vesicles models. In order to reconcile the transfer models, we propose that different mechanisms could co-exist to sustain skin pigmentation under different conditions. We also discuss the limited knowledge about melanin processing within keratinocytes. Finally, we pinpoint new questions that ought to be addressed to solve the long-lasting quest for the understanding of how basal skin pigmentation is controlled. This knowledge will allow the emergence of new strategies to treat pigmentary disorders that cause a significant socio-economic burden to patients and healthcare systems worldwide and could also have relevant cosmetic applications. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Figure 1

18 pages, 15268 KiB

Open AccessReview

Melanogenesis Connection with Innate Immunity and Toll-Like Receptors

by Saaya Koike and Kenshi Yamasaki

Int. J. Mol. Sci. 2020, 21(24), 9769; https://doi.org/10.3390/ijms21249769 - 21 Dec 2020

Cited by 29 | Viewed by 6858

Abstract

The epidermis is located in the outermost layer of the living body and is the place where external stimuli such as ultraviolet rays and microorganisms first come into contact. Melanocytes and melanin play a wide range of roles such as adsorption of metals, thermoregulation, and protection from foreign enemies by camouflage. Pigmentary disorders are observed in diseases associated with immunodeficiency such as Griscelli syndrome, indicating molecular sharing between immune systems and the machineries of pigment formation. Melanocytes express functional toll-like receptors (TLRs), and innate immune stimulation via TLRs affects melanin synthesis and melanosome transport to modulate skin pigmentation. TLR2 enhances melanogenetic gene expression to augment melanogenesis. In contrast, TLR3 increases melanosome transport to transfer to keratinocytes through Rab27A, the responsible molecule of Griscelli syndrome. TLR4 and TLR9 enhance tyrosinase expression and melanogenesis through p38 MAPK (mitogen-activated protein kinase) and NFκB signaling pathway, respectively. TLR7 suppresses microphthalmia-associated transcription factor (MITF), and MITF reduction leads to melanocyte apoptosis. Accumulating knowledge of the TLRs function of melanocytes has enlightened the link between melanogenesis and innate immune system. Full article

(This article belongs to the Special Issue Melanosome Transport/Transfer and Melanin Pigmentation in the Skin)

► Show Figures

Journal Menu

Journal Browser

Melanosome Transport/Transfer and Melanin Pigmentation in the Skin

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI