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Cells Jun 2022Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson's disease (PD). In PD, alpha-Synuclein (aSyn) has...
Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson's disease (PD). In PD, alpha-Synuclein (aSyn) has been shown to be involved in the pigmentation of neurons. The presynaptic protein is intensively investigated for its pathological role in PD, but its physiological function remains unknown. We hypothesized that aSyn is both involved in melanocytic differentiation and melanosome trafficking processes. We detected a strong expression of aSyn in human epidermal melanocytes (NHEMs) and observed its regulation in melanocytic differentiation via the microphthalmia-associated transcription factor (MITF), a central regulator of differentiation. Moreover, we investigated its role in pigmentation by performing siRNA experiments but found no effect on the total melanin content. We discovered a localization of aSyn to melanosomes, and further analysis of aSyn knockdown revealed an important role in melanocytic morphology and a reduction in melanosome release. Additionally, we found a reduction of transferred melanosomes in co-culture experiments of melanocytes and keratinocytes but no complete inhibition of melanosome transmission. In summary, this study highlights a novel physiological role of aSyn in melanocytic morphology and its so far unknown function in the pigment secretion in melanocytes.
Topics: Humans; Keratinocytes; Melanins; Melanocytes; Melanosomes; alpha-Synuclein
PubMed: 35805172
DOI: 10.3390/cells11132087 -
Cells Jun 2022Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of... (Review)
Review
Melanosomes are melanocyte-specific organelles that protect cells from ultraviolet (UV)-induced deoxyribonucleic acid damage through the production and accumulation of melanin and are transferred from melanocytes to keratinocytes. The relatively well-known process by which melanin is synthesized from melanocytes is known as melanogenesis. The relationship between melanogenesis and autophagy is attracting the attention of researchers because proteins associated with autophagy, such as WD repeat domain phosphoinositide-interacting protein 1, microtubule-associated protein 1 light chain 3, autophagy-related (ATG)7, ATG4, beclin-1, and UV-radiation resistance-associated gene, contribute to the melanogenesis signaling pathway. Additionally, there are reports that some compounds used as whitening cosmetics materials induce skin depigmentation through autophagy. Thus, the possibility that autophagy is involved in the removal of melanin has been suggested. To date, however, there is a lack of data on melanosome autophagy and its underlying mechanism. This review highlights the importance of autophagy in melanin homeostasis by providing an overview of melanogenesis, autophagy, the autophagy machinery involved in melanogenesis, and natural compounds that induce autophagy-mediated depigmentation.
Topics: Autophagy; Homeostasis; Melanins; Melanocytes; Melanosomes
PubMed: 35805169
DOI: 10.3390/cells11132085 -
Zoological Studies 2021sp. nov. is described here, and and are redescribed. Those three species are distinguished among congeners by the presence of more than 30 gill rakers on the lower...
A New Species of the Anchovy Genus Lacepède 1803 from North Sumatra, Indonesia, and Redescriptions of Baldwin 1984 and Kimura, Hori and Shibukawa 2009 (Teleostei: Clupeiformes: Engraulidae).
sp. nov. is described here, and and are redescribed. Those three species are distinguished among congeners by the presence of more than 30 gill rakers on the lower limb of the first gill arch and a short maxilla, posteriorly just reaching the anterior border of the preopercle. and have rarely been reported since they were originally described, and therefore detailed morphological data and further diagnostic characters are provided. , in turn, is described based on four specimens collected on Nias Island, North Sumatra Province, Indonesia. The new species can be distinguished from and by a shorter pectoral fin (15.6-16.3% of standard length vs. longer than 16.5%), a longer snout (4.7-4.8% of standard length vs. < 4.5%), and an intermediate number of total gill rakers on the first gill arch (63-68 in vs. 57-63 in and 72-82 in ). In addition, the new species differs from in having a dark line on the dorsum (vs. line absent), numerous melanophores laterally on the head (vs. a few melanophores on the snout and mandible tips), and higher counts of branched anal-fin rays [19-21(modally 19) vs. 17-19 (18)]. is further distinguished from by a shorter anal-fin base (22.4-22.5% of standard length vs. 22.7-25.3%).
PubMed: 35665091
DOI: 10.6620/ZS.2021.60-65 -
Journal of Dermatological Science Jun 2022Keratinocytes are recipients of melanosomes. Although the chemical basis of melanogenesis is well documented, the molecular mechanism of melanosome transfer must be...
BACKGROUND
Keratinocytes are recipients of melanosomes. Although the chemical basis of melanogenesis is well documented, the molecular mechanism of melanosome transfer must be elucidated. TRPA1 is a member of the transient receptor potential A subfamily. Previous studies have shown that inhibition of TRPA1 activity reduces melanin synthesis in human epidermal melanocytes; however, the mechanism remains unknown.
OBJECTIVE
This study aimed to investigate the roles and mechanism(s) of action of TRPA1 in keratinocytes.
METHODS
The correlation between TRPA1 expression levels and the ability of keratinocytes to phagocytize melanosomes was examined using melanin silver staining. TRPA1 depleted human epidermal keratinocytes and keratinocyte cell lines HaCaT were established using adenovirus-expressing shRNAs against TRPA1. The effects of TRPA1 on keratinocytes and HaCaT cells were determined using cell-based analyses, including light stimulation, calcium imaging, melanin phagocytosis, immunoblotting, and co-immunoprecipitation assays. The degree of epidermal pigmentation was determined in a guinea pig model.
RESULTS
TRPA1 mediated the phagocytic activity of keratinocytes. TRPA1 knockdown markedly suppressed melanosome transport to keratinocytes. Mechanistically, TRPA1 was required for PAR-2-induced melanosome phagocytosis in keratinocytes. Furthermore, TRPA1 activation indirectly stabilized microtubules by promoting the competitive binding of CYLD and acetylated α-tubulin. In addition, bortezomib (PS-341), a proteasome inhibitor, increased TRPA1 and CYLD expression and promoted phagocytic activity both in vitro and in vivo.
CONCLUSIONS
Our findings firstly suggest that TRPA1 promotes melanosome transport in keratinocytes and reveal that TRPA1 is a regulator of PAR-2 activation and microtubule stability via the PAR-2/CYLD axis.
Topics: Animals; Guinea Pigs; Keratinocytes; Melanins; Melanocytes; Melanosomes; Phagocytosis
PubMed: 35637111
DOI: 10.1016/j.jdermsci.2022.05.005 -
Scientific Reports May 2022Lower vertebrates, including fish, can rapidly alter skin lightness through changes in melanin concentration and melanosomes' mobility according to various factors,...
Lower vertebrates, including fish, can rapidly alter skin lightness through changes in melanin concentration and melanosomes' mobility according to various factors, which include background color, light intensity, ambient temperature, social context, husbandry practices and acute or chronic stressful stimuli. Within this framework, the determination of skin chromaticity parameters in fish species is estimated either in specific areas using colorimeters or at the whole animal level using image processing and analysis software. Nevertheless, the accurate quantification of melanin content or melanophore coverage in fish skin is quite challenging as a result of the laborious chemical analysis and the typical application of simple optical imaging methods, requiring also to euthanize the fish in order to obtain large skin samples for relevant investigations. Here we present the application of a novel hybrid confocal fluorescence and photoacoustic microscopy prototype for the label-free imaging and quantification of melanin in fish scales samples with high spatial resolution, sensitivity and detection specificity. The hybrid images are automatically processed through optimized algorithms, aiming at the accurate and rapid extraction of various melanin accumulation indices in large datasets (i.e., total melanin content, melanophores' area, density and coverage) corresponding to different fish species and groups. Furthermore, convolutional neural network-based algorithms have been trained using the recorded data towards the classification of different scales' samples with high accuracy. In this context, we demonstrate that the proposed methodology may increase substantially the precision, as well as, simplify and expedite the relevant procedures for the quantification of melanin content in marine organisms.
Topics: Animals; Melanins; Melanophores; Microscopy; Skin Pigmentation; Spectrum Analysis
PubMed: 35504968
DOI: 10.1038/s41598-022-11262-0 -
The Journal of Investigative Dermatology Oct 2022Sequence variation in SLC45A2 are responsible for oculocutaneous albinism type 4 in many species and are associated with melanoma susceptibility, but the molecular...
Sequence variation in SLC45A2 are responsible for oculocutaneous albinism type 4 in many species and are associated with melanoma susceptibility, but the molecular mechanism is unclear. In this study, we used Slc45a2-deficient melanocyte and mouse models to elucidate the roles of SLC45A2 in melanogenesis and melanoma metastasis. We found that the acidified cellular environment impairs the activity of key melanogenic enzyme tyrosinase in Slc45a2-deficient melanocytes. SLC45A2 is identified as a proton/glucose exporter in melanosomes, and its ablation increases the acidification of melanosomal pH through enhanced glycolysis. Intriguingly, C-glucose-labeled metabolic flux and biochemical assays show that melanosomes are active glucose-metabolizing organelles, indicating that elevated glycolysis mainly occurs in melanosomes owing to Slc45a2 deficiency. Moreover, Slc45a2 deficiency significantly upregulates the activities of glycolytic enzymes and phosphatidylinositol 3-kinase/protein kinase B signaling to promote glycolysis-dependent survival and metastasis of melanoma cells. Collectively, our study reveals that the proton/glucose exporter SLC45A2 mediates melanin synthesis and melanoma metastasis primarily by modulating melanosomal glucose metabolism.
Topics: Animals; Glucose; Glycolysis; Hydrogen-Ion Concentration; Melanins; Melanocytes; Melanoma; Melanosomes; Mice; Monophenol Monooxygenase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Protons
PubMed: 35469906
DOI: 10.1016/j.jid.2022.04.008 -
Nature Apr 2022Remarkably well-preserved soft tissues in Mesozoic fossils have yielded substantial insights into the evolution of feathers. New evidence of branched feathers in...
Remarkably well-preserved soft tissues in Mesozoic fossils have yielded substantial insights into the evolution of feathers. New evidence of branched feathers in pterosaurs suggests that feathers originated in the avemetatarsalian ancestor of pterosaurs and dinosaurs in the Early Triassic, but the homology of these pterosaur structures with feathers is controversial. Reports of pterosaur feathers with homogeneous ovoid melanosome geometries suggest that they exhibited limited variation in colour, supporting hypotheses that early feathers functioned primarily in thermoregulation. Here we report the presence of diverse melanosome geometries in the skin and simple and branched feathers of a tapejarid pterosaur from the Early Cretaceous found in Brazil. The melanosomes form distinct populations in different feather types and the skin, a feature previously known only in theropod dinosaurs, including birds. These tissue-specific melanosome geometries in pterosaurs indicate that manipulation of feather colour-and thus functions of feathers in visual communication-has deep evolutionary origins. These features show that genetic regulation of melanosome chemistry and shape was active early in feather evolution.
Topics: Animals; Biological Evolution; Dinosaurs; Feathers; Fossils; Melanosomes; Pigmentation
PubMed: 35444275
DOI: 10.1038/s41586-022-04622-3 -
Traffic (Copenhagen, Denmark) Jun 2022In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to...
In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to explain the melanin transfer mechanism, which differ essentially in how melanin is transferred-either in a membrane-bound melanosome or as a melanosome core, that is, melanocore. Here, we investigated the endocytic route followed by melanocores and melanosomes during internalization by keratinocytes, by comparing the uptake of melanocores isolated from the supernatant of melanocyte cultures, with melanosomes isolated from melanocytes. We show that inhibition of actin dynamics impairs the uptake of both melanocores and melanosomes. Moreover, depletion of critical proteins involved in actin-dependent uptake mechanisms, namely Rac1, CtBP1/BARS, Cdc42 or RhoA, together with inhibition of Rac1-dependent signaling pathways or macropinocytosis suggest that melanocores are internalized by phagocytosis, whereas melanosomes are internalized by macropinocytosis. Interestingly, we found that Rac1, Cdc42 and RhoA are differently activated by melanocore or melanosome stimulation, supporting the existence of two distinct routes of melanin internalization. Furthermore, we show that melanocore uptake induces protease-activated receptor-2 (PAR-2) internalization by keratinocytes to a higher extent than melanosomes. Because skin pigmentation was shown to be regulated by PAR-2 activation, our results further support the melanocore-based mechanism of melanin transfer and further refine this model, which can now be described as coupled melanocore exo/phagocytosis.
Topics: Actins; Keratinocytes; Melanins; Melanocytes; Melanosomes; Phagocytosis; Receptor, PAR-2
PubMed: 35426185
DOI: 10.1111/tra.12843 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2022The heart begins to form early during vertebrate development and is the first functional organ of the embryo. This study aimed to describe and compare the heart...
The heart begins to form early during vertebrate development and is the first functional organ of the embryo. This study aimed to describe and compare the heart development in three Neotropical anuran species, Physalaemus albonotatus, Elachistocleis bicolor, and Scinax nasicus. Different Gosner Stages (GS) of embryos (GS 18-20) and premetamorphic (GS 21-25), prometamorphic (GS 26-41), and metamorphic (GS 42-46) tadpoles were analyzed using stereoscopic microscopy and Scanning Electronic Microscopy. Heart development was similar in the three analyzed species; however, some heterochronic events were identified between P. albonotatus and S. nasicus compared to E. bicolor. In addition, different patterns of melanophores arrangement were observed. During the embryonic and metamorphic periods, the main morphogenetic events occur: formation of the heart tube, regionalization of the heart compartments, development of spiral valve, onset of heartbeat, looping, and final displacement of the atrium and its complete septation. Both periods are critical for the normal morphogenesis and the correct functioning of the anuran heart. These results are useful to characterize the normal anuran heart morphology and to identify possible abnormalities caused by exposure to environmental contaminants.
Topics: Animals; Organogenesis; Anura; Larva; Morphogenesis; Heart
PubMed: 35412699
DOI: 10.1002/ar.24933 -
Cancers Mar 2022Melanin is the pigment that protects DNA from ultraviolet (UV) damage by absorbing excess energy. Melanin is produced in a process called melanogenesis. When... (Review)
Review
Melanin is the pigment that protects DNA from ultraviolet (UV) damage by absorbing excess energy. Melanin is produced in a process called melanogenesis. When melanogenesis is altered, diseases such as albinism result. Albinism can result in an increased skin cancer risk. Conversely, black pigment cell (melanocyte) development pathways can be misregulated, causing excessive melanocyte growth that leads to melanoma (cancer of melanocytes). Zebrafish is an emerging model organism used to study pigment disorders due to their high fecundity, visible melanin development in melanophores (melanocytes in mammals) from 24 h post-fertilization, and conserved melanogenesis pathways. Here, we reviewed the conserved developmental pathways in zebrafish melanophores and mammalian melanocytes. Additionally, we summarized the progress made in understanding pigment cell disease and evidence supporting the strong potential for using zebrafish to find novel treatment options for albinism.
PubMed: 35406524
DOI: 10.3390/cancers14071752