Chemical Composition and Terminology Of Specialized Organelles (Melanosomes and Melanin Granules) in Mammalian Melanocytes

Seiji, Makoto; Fitzpatrick, Thomas B.; Simpson, Robert T.; Birbeck, M. S. C.

doi:10.1038/1971082a0

Cited by 158 publications

(109 citation statements)

References 17 publications

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“…Second, a potential organocopper biomarker for melanin was previously detected in this specimen; this biomarker has also been correlated with the presence of melanosomes in three fossil bird taxa 25 . We hypothesize that melanosome structures fossilize simply by virtue of being solid aggregations of melanins [26][27][28] , which themselves have high preservation potential 29 as large, insoluble polymers resistant to degradation 4 . Third, the dark trace is associated with sulphur ( Fig.…”

Section: Identitymentioning

confidence: 99%

New evidence on the colour and nature of the isolated Archaeopteryx feather

et al. 2012

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Archaeopteryx has been regarded as an icon of evolution ever since its discovery from the Late Jurassic limestone deposits of solnhofen, Germany in 1861. Here we report the first evidence of colour from Archaeopteryx based on fossilized colour-imparting melanosomes discovered in this isolated feather specimen. using a phylogenetically diverse database of extant bird feathers, statistical analysis of melanosome morphology predicts that the original colour of this Archaeopteryx feather was black, with 95% probability. Furthermore, reexamination of the feather's morphology leads us to interpret it as an upper major primary covert, contrary to previous interpretations. Additional findings reveal that the specimen is preserved as an organosulphur residue, and that barbule microstructure identical to that of modern bird feathers had evolved as early as the Jurassic. As in extant birds, the extensive melanization would have provided structural advantages to the Archaeopteryx wing feather during this early evolutionary stage of dinosaur flight.

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Section: Identitymentioning

confidence: 99%

New evidence on the colour and nature of the isolated Archaeopteryx feather

et al. 2012

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“…Melanosome stages were defined by morphology (22,43). Quantification of the length and width of melanosomes was determined by using iTEM software (Soft Imaging System).…”

Section: Emmentioning

confidence: 99%

BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells

Rochin

Hurbain

Serneels

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

145

166

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Amyloids are often associated with pathologic processes such as in Alzheimer's disease (AD), but can also underlie physiological processes such as pigmentation. Formation of pathological and functional amyloidogenic substrates can require precursor processing by proteases, as exemplified by the generation of Aβ peptide from amyloid precursor protein (APP) by beta-site APP cleaving enzyme (BACE)1 and γ-secretase. Proteolytic processing of the pigment cell-specific Melanocyte Protein (PMEL) is also required to form functional amyloid fibrils during melanogenesis, but the enzymes involved are incompletely characterized. Here we show that the BACE1 homologue BACE2 processes PMEL to generate functional amyloids. BACE2 is highly expressed in pigment cells and Bace2 −/− but not Bace1 −/− mice display coat color defects, implying a specific role for BACE2 during melanogenesis. By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. These studies identify an amyloidogenic substrate of BACE2, reveal an important physiological role for BACE2 in pigmentation, and highlight analogies in the generation of PMEL-derived functional amyloids and APPderived pathological amyloids.

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“…Melanosomes undergo a well-characterized series of morphologically recognizable maturational stages during formation (10,11). Stage I is characterized by intralumenal vesicles; stage II develops an elliptic shape and intralumenal longitudinal fibrils; stage III has evidence of pigment deposition along the fibrils; stage IV melanosomes are filled with pigment, obscuring the fibrils completely (see Fig.…”

Section: Introductionmentioning

confidence: 99%

Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes

et al. 2009

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Whereas resistance to chemotherapy has long impeded effective treatment of metastatic melanoma, the mechanistic basis of this resistance remains unknown. One possible mechanism of drug resistance is alteration of intracellular drug distribution either by drug efflux or sequestration into intracellular organelles. Melanomas, as well as primary melanocytes from which they arise, have intracellular organelles, called melanosomes, wherein the synthesis and storage of the pigment melanin takes place. In this study, comparisons of congenic cells with and without functional molecules regulating melanosome formation show that sensitivity to the chemotherapeutic agent cis-diaminedichloroplatinum II (cis-platin) significantly increases with the mutation of genes regulating melanosome formation, concomitant disruption of melanosome morphology, and loss of mature melanosomes. Absence of the melanosomal structural protein gp100/Pmel17 causes increased cis-platin sensitivity. Independent mutations in three separate genes that regulate melanosome biogenesis (Dtnbp1, Pldn, Vps33a) also result in increased cis-platin sensitivity. In addition, a mutation of the gene encoding the integral melanosomal protein tyrosinase, resulting in aberrant melanosome formation, also causes increased cis-platin sensitivity. Furthermore, sensitivity to agents in other chemotherapeutic classes (e.g., vinblastine and etoposide) also increased with the mutation of Pldn. In contrast, a mutation in another melanosomal regulatory gene, Hps1, minimally affects melanosome biogenesis, preserves the formation of mature melanosomes, and has no effect on cis-platin or vinblastine response. Together, these data provide the first direct evidence that melanosomal regulatory genes influence drug sensitivity and that the presence of mature melanosomes likely contributes to melanoma resistance to therapy. [Cancer Res 2009;69(3):992-9]

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Chemical Composition and Terminology Of Specialized Organelles (Melanosomes and Melanin Granules) in Mammalian Melanocytes

Cited by 158 publications

References 17 publications

New evidence on the colour and nature of the isolated Archaeopteryx feather

New evidence on the colour and nature of the isolated Archaeopteryx feather

BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells

Multidrug Resistance Decreases with Mutations of Melanosomal Regulatory Genes

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