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Pigment Cell & Melanoma Research Mar 2021Melanosomes are specialized intracellular organelles that produce and store melanin pigments in melanocytes, which are present in several mammalian tissues and organs,... (Review)
Review
Melanosomes are specialized intracellular organelles that produce and store melanin pigments in melanocytes, which are present in several mammalian tissues and organs, including the skin, hair, and eyes. Melanosomes form and mature stepwise (stages I-IV) in melanocytes and then are transported toward the plasma membrane along the cytoskeleton. They are subsequently transferred to neighboring keratinocytes by a largely unknown mechanism, and incorporated melanosomes are transported to the perinuclear region of the keratinocytes where they form melanin caps. Melanocytes also extend several dendrites that facilitate the efficient transfer of the melanosomes to the keratinocytes. Since the melanosome biogenesis, transport, and transfer steps require multiple membrane trafficking processes, Rab GTPases that are conserved key regulators of membrane traffic in all eukaryotes are crucial for skin and hair pigmentation. Dysfunctions of two Rab isoforms, Rab27A and Rab38, are known to cause a hypopigmentation phenotype in human type 2 Griscelli syndrome patients and in chocolate mice (related to Hermansky-Pudlak syndrome), respectively. In this review article, I review the literature on the functions of each Rab isoform and its upstream and downstream regulators in mammalian melanocytes and keratinocytes.
Topics: Animals; Humans; Melanins; Melanocytes; Melanosomes; Protein Transport; rab GTP-Binding Proteins
PubMed: 32997883
DOI: 10.1111/pcmr.12931 -
The Journal of Investigative Dermatology Feb 2020Pigmentation of the skin and hair represents the result of melanin biosynthesis within melanosomes of epidermal melanocytes, followed by the transfer of mature melanin... (Review)
Review
Pigmentation of the skin and hair represents the result of melanin biosynthesis within melanosomes of epidermal melanocytes, followed by the transfer of mature melanin granules to adjacent keratinocytes within the basal layer of the epidermis. Natural variation in these processes produces the diversity of skin and hair color among human populations, and defects in these processes lead to diseases such as oculocutaneous albinism. While genetic regulators of pigmentation have been well studied in human and animal models, we are still learning much about the cell biological features that regulate melanogenesis, melanosome maturation, and melanosome motility in melanocytes, and have barely scratched the surface in our understanding of melanin transfer from melanocytes to keratinocytes. Herein, we describe cultured cell model systems and common assays that have been used by investigators to dissect these features and that will hopefully lead to additional advances in the future.
Topics: Animals; Cell Culture Techniques; Coculture Techniques; Humans; Image Processing, Computer-Assisted; Intravital Microscopy; Keratinocytes; Melanins; Melanosomes; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Pigmentation Disorders; Research Design; Skin Pigmentation; Spectrophotometry
PubMed: 31980058
DOI: 10.1016/j.jid.2019.12.002 -
Current Biology : CB Sep 2020At oceanic depths >200 m, there is little ambient sunlight, but bioluminescent organisms provide another light source that can reveal animals to visual predators and...
At oceanic depths >200 m, there is little ambient sunlight, but bioluminescent organisms provide another light source that can reveal animals to visual predators and prey [1-4]. Transparency and mirrored surfaces-common camouflage strategies under the diffuse solar illumination of shallower waters-are conspicuous when illuminated by directed bioluminescent sources due to reflection from the body surface [5, 6]. Pigmentation allows animals to absorb light from bioluminescent sources, rendering them visually undetectable against the dark background of the deep sea [5]. We present evidence suggesting pressure to reduce reflected bioluminescence led to the evolution of ultra-black skin (reflectance <0.5%) in 16 species of deep-sea fishes across seven distantly related orders. Histological data suggest this low reflectance is mediated by a continuous layer of densely packed melanosomes in the exterior-most layer of the dermis [7, 8] and that this layer lacks the unpigmented gaps between pigment cells found in other darkly colored fishes [9-13]. Using finite-difference, time-domain modeling and comparisons with melanosomes found in other ectothermic vertebrates [11, 13-21], we find the melanosomes making up the layer in these ultra-black species are optimized in size and shape to minimize reflectance. Low reflectance results from melanosomes scattering light within the layer, increasing the optical path length and therefore light absorption by the melanin. By reducing reflectance, ultra-black fish can reduce the sighting distance of visual predators more than 6-fold compared to fish with 2% reflectance. This biological example of efficient light absorption via a simple architecture of strongly absorbing and highly scattering particles may inspire new ultra-black materials.
Topics: Adaptation, Physiological; Animals; Biological Mimicry; Color; Fishes; Melanins; Melanosomes; Oceans and Seas; Skin Pigmentation
PubMed: 32679102
DOI: 10.1016/j.cub.2020.06.044 -
Experimental Dermatology Apr 2023Melatonin influences mammalian coat colour and hair follicle pigmentation and also weakly alters the electrical stimulation of retinal cells in the eyes. A direct... (Review)
Review
Melatonin influences mammalian coat colour and hair follicle pigmentation and also weakly alters the electrical stimulation of retinal cells in the eyes. A direct melanocytic response to melatonin is still uncertain in mammals and human skin pigmentation. Melatonin acts as a free radical scavenger and thus inhibits the initiation of cancer cell growth. Treatment of melanoma sees perspective features in the administration of melatonin along with known chemotherapeutic molecules to improve the efficacy of conventional cytotoxic agents. Being richly supplied with a variety of receptors, melanocytes and melanoma cells can be used as in vitro test models for pharmacological applications of known and novel drugs.
Topics: Animals; Humans; Melatonin; Melanocytes; Melanoma; Hair Follicle; Pigmentation Disorders; Mammals
PubMed: 36437610
DOI: 10.1111/exd.14715 -
Genome Biology and Evolution Jul 2021Color and color pattern are critical for animal camouflage, reproduction, and defense. Few studies, however, have attempted to identify candidate genes for color and...
Color and color pattern are critical for animal camouflage, reproduction, and defense. Few studies, however, have attempted to identify candidate genes for color and color pattern in squamate reptiles, a colorful group with over 10,000 species. We used comparative transcriptomic analyses between white, orange, and yellow skin in a color-polymorphic species of anole lizard to 1) identify candidate color and color-pattern genes in squamates and 2) assess if squamates share an underlying genetic basis for color and color pattern variation with other vertebrates. Squamates have three types of chromatophores that determine color pattern: guanine-filled iridophores, carotenoid- or pteridine-filled xanthophores/erythrophores, and melanin-filled melanophores. We identified 13 best candidate squamate color and color-pattern genes shared with other vertebrates: six genes linked to pigment synthesis pathways, and seven genes linked to chromatophore development and maintenance. In comparisons of expression profiles between pigment-rich and white skin, pigment-rich skin upregulated the pteridine pathway as well as xanthophore/erythrophore development and maintenance genes; in comparisons between orange and yellow skin, orange skin upregulated the pteridine and carotenoid pathways as well as melanophore maintenance genes. Our results corroborate the predictions that squamates can produce similar colors using distinct color-reflecting molecules, and that both color and color-pattern genes are likely conserved across vertebrates. Furthermore, this study provides a concise list of candidate genes for future functional verification, representing a first step in determining the genetic basis of color and color pattern in anoles.
Topics: Animals; Chromatophores; Lizards; Melanophores; Skin; Skin Pigmentation; Transcriptome
PubMed: 33988681
DOI: 10.1093/gbe/evab110 -
ELife Dec 2021The brilliant iridescent plumage of birds creates some of the most stunning color displays known in the natural world. Iridescent plumage colors are produced by...
The brilliant iridescent plumage of birds creates some of the most stunning color displays known in the natural world. Iridescent plumage colors are produced by nanostructures in feathers and have evolved in diverse birds. The building blocks of these structures-melanosomes (melanin-filled organelles)-come in a variety of forms, yet how these different forms contribute to color production across birds remains unclear. Here, we leverage evolutionary analyses, optical simulations, and reflectance spectrophotometry to uncover general principles that govern the production of brilliant iridescence. We find that a key feature that unites all melanosome forms in brilliant iridescent structures is thin melanin layers. Birds have achieved this in multiple ways: by decreasing the size of the melanosome directly, by hollowing out the interior, or by flattening the melanosome into a platelet. The evolution of thin melanin layers unlocks color-producing possibilities, more than doubling the range of colors that can be produced with a thick melanin layer and simultaneously increasing brightness. We discuss the implications of these findings for the evolution of iridescent structures in birds and propose two evolutionary paths to brilliant iridescence.
Topics: Animals; Biological Evolution; Birds; Color; Feathers; Iridescence; Melanins; Melanosomes; Microscopy, Electron, Transmission
PubMed: 34930526
DOI: 10.7554/eLife.71179 -
Current Opinion in Cell Biology Dec 2020Melanocytes are neuroectoderm-derived pigment-producing cells with highly polarized dendritic morphology. They protect the skin against ultraviolet radiation by... (Review)
Review
Melanocytes are neuroectoderm-derived pigment-producing cells with highly polarized dendritic morphology. They protect the skin against ultraviolet radiation by providing melanin to neighbouring keratinocytes. However, the mechanisms underlying melanocyte polarization and its relevance for diseases remain mostly elusive. Numerous studies have instead revealed roles for polarity regulators in other neuroectoderm-derived lineages including different neuronal cell types. Considering the shared ontogeny and morphological similarities, these lineages may be used as reference models for the exploration of melanocyte polarity, for example, regarding dendrite formation, spine morphogenesis and polarized organelle transport. In this review, we summarize and compare the latest progress in understanding polarity regulation in neuronal cells and melanocytes and project key open questions for future work.
Topics: Cell Differentiation; Cell Lineage; Cell Polarity; Humans; Keratinocytes; Melanocytes; Melanosomes; Neural Plate
PubMed: 33099084
DOI: 10.1016/j.ceb.2020.09.001 -
The Journal of Biological Chemistry Aug 2023Niemann-Pick type C1 (NPC1) protein is a multimembrane spanning protein of the lysosome limiting membrane that facilitates intracellular cholesterol and sphingolipid...
Niemann-Pick type C1 (NPC1) protein is a multimembrane spanning protein of the lysosome limiting membrane that facilitates intracellular cholesterol and sphingolipid transport. Loss-of-function mutations in the NPC1 protein cause Niemann-Pick disease type C1, a lysosomal storage disorder characterized by the accumulation of cholesterol and sphingolipids within lysosomes. To investigate whether the NPC1 protein could also play a role in the maturation of the endolysosomal pathway, here, we have investigated its role in a lysosome-related organelle, the melanosome. Using a NPC1-KO melanoma cell model, we found that the cellular phenotype of Niemann-Pick disease type C1 is associated with a decreased pigmentation accompanied by low expression of the melanogenic enzyme tyrosinase. We propose that the defective processing and localization of tyrosinase, occurring in the absence of NPC1, is a major determinant of the pigmentation impairment in NPC1-KO cells. Along with tyrosinase, two other pigmentation genes, tyrosinase-related protein 1 and Dopachrome-tautomerase have lower protein levels in NPC1 deficient cells. In contrast with the decrease in pigmentation-related protein expression, we also found a significant intracellular accumulation of mature PMEL17, the structural protein of melanosomes. As opposed to the normal dendritic localization of melanosomes, the disruption of melanosome matrix generation in NPC1 deficient cells causes an accumulation of immature melanosomes adjacent to the plasma membrane. Together with the melanosomal localization of NPC1 in WT cells, these findings suggest that NPC1 is directly involved in tyrosinase transport from the trans-Golgi network to melanosomes and melanosome maturation, indicating a novel function for NPC1.
Topics: Humans; Melanosomes; Monophenol Monooxygenase; Niemann-Pick C1 Protein; Cholesterol; Niemann-Pick Diseases; Niemann-Pick Disease, Type C
PubMed: 37423302
DOI: 10.1016/j.jbc.2023.105024 -
Comparative Biochemistry and... Mar 2022Oscar Astronotus ocellatus is an important ornamental fish, including albino and wild varieties. Albino individuals attract aquarium hobbyists due to their unique body...
Oscar Astronotus ocellatus is an important ornamental fish, including albino and wild varieties. Albino individuals attract aquarium hobbyists due to their unique body color, but studies on the species' albinism mechanism are currently scarce. Here, we investigated the morphological and transcriptomic profiles of the skin of albino and wild Oscar. The results showed that the albino type had fewer oval-shaped melanophores and immature melanosomes but that the wild type contained more stellate-shaped melanophores and mature melanosomes. Albino Oscar had a degenerative pigment layer without obvious melanin deposition and content, while the wild type contained more concentrated melanin within the pigment layer. A total of 272,392 unigenes were detected, 109 of which were identified as differentially expressed genes (DEGs) between albino and wild Oscar. Pathways of DEGs, including those involved in complement and coagulation cascades, novobiocin biosynthesis, Th1 and Th2 cell differentiation, and tropane, piperidine and pyridine alkaloid biosynthesis, were significantly enriched. DEGs, including upregulated Sfrp5 and Tat, and downregulated Wnt-10a, Ppp3c, Notch1 and Trim27 involved in the Wnt signaling pathway, Notch signaling pathway, tyrosine metabolism, MAPK signaling pathway and melanogenesis, might be associated with the albinism of Oscar. This study characterized the difference in melanophore morphology between wild and albino Oscar and identified some albinism-related candidate genes and signaling pathways, helping to understand the genetic mechanism of fish albinism.
Topics: Albinism; Animals; Cichlids; Melanins; Skin; Transcriptome
PubMed: 34864613
DOI: 10.1016/j.cbd.2021.100944 -
Biochimica Et Biophysica Acta.... Dec 2020Melanosomes are unique organelles in melanocytes that produce melanin, the pigment for skin, hair, and eye color. Tyrosinase is the essential and rate-limiting enzyme... (Review)
Review
Melanosomes are unique organelles in melanocytes that produce melanin, the pigment for skin, hair, and eye color. Tyrosinase is the essential and rate-limiting enzyme for melanin production, that strictly requires neutral pH for activity. pH maintenance is a result of the combinational function of multiple ion transport proteins. Thus, ion homeostasis in melanosomes is crucial for melanin synthesis. Defect of the ion transport system causes various pigmentation phenotypes, from mild effect to severe disorders such as albinism. In this review, we summarize the up-to-date knowledge of the ion transport system, such as transport function, structure, and the physiological roles and mechanisms of the ion transport proteins in melanosomes. In addition, we propose a model of melanosomal ion transport system-how the functional coupling of multiple transport proteins modulates and maintains ion homeostasis. We discuss melanin synthesis in terms of the ion transport system.
Topics: Albinism, Oculocutaneous; Humans; Hydrogen-Ion Concentration; Ion Transport; Lysosomes; Melanins; Melanosomes; Membrane Transport Proteins; Monophenol Monooxygenase; Skin Pigmentation
PubMed: 32333855
DOI: 10.1016/j.bbamem.2020.183318