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Pharmacology & Therapeutics Mar 2021Melanosomes are specialized membrane-bound organelles that synthesize and organize melanin, ultimately providing color to the skin, hair, and eyes. Disorders in... (Review)
Review
Melanosomes are specialized membrane-bound organelles that synthesize and organize melanin, ultimately providing color to the skin, hair, and eyes. Disorders in melanogenesis and melanosome transport are linked to pigmentary diseases, such as Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Griscelli syndrome. Clinical cases of these pigmentary diseases shed light on the molecular mechanisms that control melanosome-related pathways. However, only an improved understanding of melanogenesis and melanosome transport will further the development of diagnostic and therapeutic approaches. Herein, we review the current literature surrounding melanosomes with particular emphasis on melanosome membrane transport and cytoskeleton-mediated melanosome transport. We also provide perspectives on melanosome regulatory mechanisms which include hormonal action, inflammation, autophagy, and organelle interactions.
Topics: Autophagy; Biological Transport; Humans; Melanins; Melanosomes; Signal Transduction
PubMed: 33075361
DOI: 10.1016/j.pharmthera.2020.107707 -
Integrative and Comparative Biology Oct 2021Melanins, the main pigments of the skin and hair in mammals, are synthesized within membrane-bound organelles of melanocytes called melanosomes. Melanosome structure and... (Review)
Review
Melanins, the main pigments of the skin and hair in mammals, are synthesized within membrane-bound organelles of melanocytes called melanosomes. Melanosome structure and function are determined by a cohort of resident transmembrane proteins, many of which are expressed only in pigment cells and localize specifically to melanosomes. Defects in the genes that encode melanosome-specific proteins or components of the machinery required for their transport in and out of melanosomes underlie various forms of ocular or oculocutaneous albinism, characterized by hypopigmentation of the hair, skin, and eyes and by visual impairment. We review major components of melanosomes, including the enzymes that catalyze steps in melanin synthesis from tyrosine precursors, solute transporters that allow these enzymes to function, and structural proteins that underlie melanosome shape and melanin deposition. We then review the molecular mechanisms by which these components are biosynthetically delivered to newly forming melanosomes-many of which are shared by other cell types that generate cell type-specific lysosome-related organelles. We also highlight unanswered questions that need to be addressed by future investigation.
Topics: Animals; Mammals; Melanins; Melanocytes; Melanosomes; Pigmentation
PubMed: 34021746
DOI: 10.1093/icb/icab078 -
Biochemical Society Transactions Aug 2018Historically, studies on the maturation and intracellular transport of melanosomes in melanocytes have greatly contributed to elucidating the general mechanisms of... (Review)
Review
Historically, studies on the maturation and intracellular transport of melanosomes in melanocytes have greatly contributed to elucidating the general mechanisms of intracellular transport in many different types of mammalian cells. During melanosome maturation, melanosome cargoes including melanogenic enzymes (e.g. tyrosinase) are transported from endosomes to immature melanosomes by membrane trafficking, which must require a membrane fusion process likely regulated by SNAREs [oluble SF (-ethylmaleimide-sensitive factor) ttachment protein ceptors]. In the present study, we review the literature concerning the expression and function of SNAREs (e.g. v-SNARE vesicle-associated membrane protein 7 and t-SNAREs syntaxin-3/13 and synaptosomal-associated protein-23) in melanocytes, especially in regard to the fusion process in which melanosome cargoes are finally delivered to immature melanosomes. We also describe the recent discovery of the SNARE recycling system on mature melanosomes in melanocytes. Such SNARE dynamics, especially the SNARE recycling system, on melanosomes will be useful in understanding as yet unidentified SNARE dynamics on other organelles.
Topics: Animals; Carrier Proteins; Humans; Melanosomes; Membrane Fusion; Organelles; Protein Transport; SNARE Proteins
PubMed: 30026369
DOI: 10.1042/BST20180130 -
Current Opinion in Cell Biology Aug 2014The pigmentation of skin and hair in mammals is driven by the creation within melanocytes of melanosomes, a specialized pigment-producing organelle, and the subsequent... (Review)
Review
The pigmentation of skin and hair in mammals is driven by the creation within melanocytes of melanosomes, a specialized pigment-producing organelle, and the subsequent intercellular transfer of this organelle to keratinocytes. This latter process is absolutely required for visible pigmentation and effective photo-protection because it serves to disperse the pigment in skin and hair. Therefore, the transfer of melanosomes from the melanocyte to the keratinocyte is as important for the biological endpoint of mammalian pigmentation as the biogenesis of this fascinating organelle. Here we review new findings that shed light on, and raise additional questions about, the mechanism of this enigmatic process.
Topics: Animals; Endocytosis; Exocytosis; Hair; Humans; Melanosomes; Skin; Skin Physiological Phenomena
PubMed: 24662021
DOI: 10.1016/j.ceb.2014.02.003 -
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 -
Pigment Cell Research Jun 2003Our mini review summarizes what is known about the (bio)degradation of melanosomes. Unlike melanosome biogenesis where our knowledge enables us to explain it in... (Review)
Review
Our mini review summarizes what is known about the (bio)degradation of melanosomes. Unlike melanosome biogenesis where our knowledge enables us to explain it in molecular terms posing many interesting questions on the relation between lysosomes and melanosomes, melanosome degradation has remained 'terra incognita'. Observations at optical and ultrastructural levels describe the disintegration of melanosomes in the lysosomal compartment (in auto- and heterophagosomes). Histochemical studies suggest the participation of acid hydrolases in the process of melanosome degradation. Biochemical data confirm the ability of lysosomal hydrolases to degrade melanosome constituents except the melanin moiety. The similarity of melanin structure to that of polycyclic aromatic hydrocarbons suggests that melanin should be sensitive mainly, if not exclusively, to oxidative breakdown. In vitro melanin can indeed be decomposed by an oxidative attack and the degradation is accompanied by fluorescence and decreasing absorbance. From enzymes engaged in the biotransformation of polycyclic hydrocarbons only phagosomal NADPH oxidase meets the criteria (particularly as for compartmental and catalytic properties) to be involved in melanin biodegradation. The in vivo biodegradation of melanin has so far been clearly demonstrated in Aspergillus and fungi melanins.
Topics: Animals; Humans; Hydrolysis; Lysosomes; Melanins; Melanocytes; Melanoma, Experimental; Melanosomes; Mice; NADPH Oxidases; Oxidation-Reduction; Oxygen; Phagosomes; Polycyclic Aromatic Hydrocarbons; Spectrophotometry
PubMed: 12753402
DOI: 10.1034/j.1600-0749.2003.00040.x -
Experimental Dermatology 2003Complexion coloration in humans is primarily regulated by the amount and type of melanin synthesized by the epidermal melanocyte. However, additional and equally... (Review)
Review
Complexion coloration in humans is primarily regulated by the amount and type of melanin synthesized by the epidermal melanocyte. However, additional and equally contributing factors consist of (1) efficient transfer of melanin from the melanocytes to the neighboring keratinocytes and (2) distribution and degradation of the transferred melanosomes by the recipient keratinocytes. Once synthesized in the cell body of the epidermal melanocyte, pigmented melanosomes are translocated down the dendrites and captured at the dendritic tips via various cytoskeletal elements. Molecules recently identified that participate in this process consist of Rab27a, myosin-Va and melanophilin. Eventually, these peripherally localized melanosomes are transferred to keratinocytes by a presently undefined mechanism. The protease-activated receptor-2 (PAR-2) and unidentified surface lectins and glycoproteins facilitate this transfer process. Once incorporated into the keratinocytes, melanosomes are distributed individually or as clusters, aggregated towards the apical pole of the nucleus, and degraded as the keratinocytes undergo terminal differentiation and desquamation. Ultraviolet irradiation (UVR) can modulate the process of melanosome transfer from the melanocytes to the keratinocytes. UVR can upregulate expression of PAR-2 and lectin-binding receptors and increase phagocytic activity of cultured keratinocytes. Therefore, many cellular and molecular events that occur after melanogenesis contribute to skin color.
Topics: Biological Transport; Dendrites; Humans; Keratinocytes; Melanins; Melanosomes; Skin; Tissue Distribution; Ultraviolet Rays
PubMed: 14756517
DOI: 10.1034/j.1600-0625.12.s2.1.x -
Methods in Molecular Biology (Clifton,... 2022Several model systems have been developed to investigate mechanisms and regulation of intracellular organelle motility. The fish retinal pigment epithelial (RPE) cell...
Several model systems have been developed to investigate mechanisms and regulation of intracellular organelle motility. The fish retinal pigment epithelial (RPE) cell represents an unusual but simple system for the study of actin-dependent organelle motility. Primary cultures of RPE dissociated from the eye are amenable to motility studies using a simple perfusion chamber and conventional phase contrast microscopy. In vivo, melanin-containing pigment granules (melanosomes) within fish RPE migrate distances up to 100 μm in response to light flux. When sheets of RPE are removed from the eye and dissociated, they attach to the substrate with apical projections extending radially from the central cell body. Melanosomes can be chemically triggered to aggregate or disperse throughout the projections. Melanosome migration in RPE apical projections is dependent on actin filaments and thus renders this model system useful for investigations of actin-dependent organelle motility.
Topics: Actins; Animals; Melanosomes; Perciformes; Pigment Epithelium of Eye; Retinal Pigments
PubMed: 34542860
DOI: 10.1007/978-1-0716-1661-1_15 -
Trends in Cell Biology Oct 2003Melanosomes are specialized intracellular organelles in which melanin pigments are synthesized and stored. The ontogenesis of these morphologically unique organelles, as... (Review)
Review
Melanosomes are specialized intracellular organelles in which melanin pigments are synthesized and stored. The ontogenesis of these morphologically unique organelles, as well as their relationship to "conventional" organelles of the secretory and endocytic pathways, has for decades been a matter of study - and controversy. Recent work by the groups of Michael Marks and Graça Raposo has uncovered the molecular mechanism that results in the formation of the lumenal striations characteristic of melanosome precursor organelles.
Topics: Humans; Melanosomes; Membrane Glycoproteins; Proteins; gp100 Melanoma Antigen
PubMed: 14507476
DOI: 10.1016/j.tcb.2003.08.001 -
Nature Reviews. Molecular Cell Biology Oct 2001Melanosomes are morphologically and functionally unique organelles within which melanin pigments are synthesized and stored. Melanosomes share some characteristics with... (Review)
Review
Melanosomes are morphologically and functionally unique organelles within which melanin pigments are synthesized and stored. Melanosomes share some characteristics with lysosomes, but can be distinguished from them in many ways. The biogenesis and intracellular movement of melanosomes and related organelles are disrupted in several genetic disorders in mice and humans. The recent characterization of genes defective in these diseases has reinvigorated interest in the melanosome as a model system for understanding the molecular mechanisms that underlie intracellular membrane dynamics.
Topics: Animals; Cytoskeleton; Humans; Melanocytes; Melanosomes; Membrane Fusion; Mice; Models, Biological; Movement; Organelles
PubMed: 11584301
DOI: 10.1038/35096009