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Melanocytes are
melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
-producing neural crest-derived
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges,
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
s, and
heart The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...
. Melanin is a dark
pigment A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compou ...
primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against
UV radiation Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiatio ...
. Melanocytes also have a role in the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
.


Function

Through a process called melanogenesis, melanocytes produce
melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
, which is a pigment found in the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
, eyes, hair,
nasal cavity The nasal cavity is a large, air-filled space above and behind the nose in the middle of the face. The nasal septum divides the cavity into two cavities, also known as fossae. Each cavity is the continuation of one of the two nostrils. The nasal ...
, and inner ear. This melanogenesis leads to a long-lasting pigmentation, which is in contrast to the pigmentation that originates from oxidation of already-existing melanin. There are both basal and activated levels of melanogenesis; in general, lighter-skinned people have low basal levels of melanogenesis. Exposure to UV-B radiation causes increased melanogenesis. The purpose of melanogenesis is to protect the hypodermis, the layer under the skin, from damage by UV radiation. The color of the melanin is black, allowing it to absorb a majority of the UV light and block it from passing through the epidermis. Since the action spectrum of sunburn and melanogenesis are virtually identical, they are assumed to be induced by the same mechanism. The agreement of the action spectrum with the absorption spectrum of DNA points towards the formation of cyclobutane pyrimidine dimers (CPDs) - direct DNA damage. Typically, between 1000 and 2000 melanocytes are found per square millimeter of skin or approximately 5% to 10% of the cells in the basal layer of epidermis. Although their size can vary, melanocytes are typically 7 μm in length. The difference in skin color between lightly and darkly pigmented individuals is due not to the number (quantity) of melanocytes in their skin, but to the melanocytes' level of activity (quantity and relative amounts of
eumelanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the am ...
and
pheomelanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the am ...
). This process is under hormonal control, including the MSH and ACTH peptides that are produced from the precursor proopiomelanocortin. Vitiligo is a skin disease where people lack melanin in certain areas in the skin. People with oculocutaneous albinism typically have a very low level of melanin production. Albinism is often but not always related to the ''TYR'' gene coding the tyrosinase enzyme. Tyrosinase is required for melanocytes to produce melanin from the
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
. Albinism may be caused by a number of other genes as well, like ''OCA2'', ''SLC45A2'', ''TYRP1'', and ''HPS1'' to name some. In all, already 17 types of oculocutaneous albinism have been recognized. Each gene is related to different protein having a role in pigment production. People with Chédiak–Higashi syndrome have a buildup of melanin granules due to abnormal function of
microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27  nm and have an inner diameter between 11 a ...
.


Role in the immune system

In addition to their role as UV radical scavengers, melanocytes are also part of the immune system, and are considered to be immune cells. Although the full role of melanocytes in immune response is not fully understood, melanocytes share many characteristics with
dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. Th ...
s: branched morphology; phagocytic capabilities; presentation of
antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respon ...
s to T-cells; and production and release of
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
s. Although melanocytes are dendritic in form and share many characteristics with dendritic cells, they are derived from two different cell lineages. Dendritic cells are derived from
hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...
s in the bone marrow. Melanocytes on the other hand originate from
neural crest cells Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, Per ...
. As such, although morphologically and functionally similar, melanocytes and dendritic cells are not the same. Melanocytes are capable of expressing
MHC Class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cell ...
, a type of MHC expressed only by certain antigen presenting cells of the immune system, when stimulated by interactions with antigen or cytokines. All cells in any given vertebrate express MHC, but most cells only express MHC class I. The other class of MHC, Class II, is found only on "professional" antigen presenting cells such as dendritic cells,
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
s, B cells, and melanocytes. Importantly, melanocytes stimulated by cytokines express surface proteins such as CD40 and ICAM1 in addition to MHC class II, allowing for co-stimulation of T cells. In addition to presenting antigen, one of the roles of melanocytes in the immune response is cytokine production. Melanocytes express many proinflammatory cytokines including IL-1, IL-3, IL-6, IL-8, TNF-α, and
TGF-β Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other s ...
. Like other immune cells, melanocytes secrete these cytokines in response to activation of
Pattern Recognition Receptors Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells o ...
(PRRs) such as Toll Like Receptor 4 (TLR4) which recognize MAMPs. MAMPs, also known as PAMPs, are microbial associated molecular patterns, small molecular elements such as proteins, carbohydrates, and lipids present on or in a given pathogen. In addition, cytokine production by melanocytes can be triggered by cytokines secreted by other nearby immune cells. Melanocytes are ideally positioned in the epidermis to be sentinels against harmful pathogens. Melanocytes reside in the stratum basale, the lowest layer of the epidermis, but they use their dendrites to interact with cells in other layers, and to capture pathogens that enter the epidermis. Melanocytes likely work in concert with both keratinocytes and Langerhans cells, both of which are also actively phagocytic, to contribute to the immune response.


Melanogenesis

Tyrosine is the non-essential amino acid precursor of melanin. Tyrosine is converted to dihydroxyphenylalanine (DOPA) via the enzyme tyrosinase. Then DOPA is polymerized into melanin. The copper-ion based enzyme-catalyzed oxidative transformation of catechol derivative dopa to light absorbing dopaquinone to indole-5,6-qionone is clearly seen following the polymerization to melanin, the color of the pigment ranges from red to dark brown.


Stimulation

Numerous stimuli are able to alter melanogenesis, or the production of melanin by cultured melanocytes, although the method by which it works is not fully understood. Certain melanocortins have been shown in laboratory testing to have effect on appetite and sexual activity in mice. Eicosanoids,
retinoids The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughou ...
,
oestrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activ ...
s,
melanocyte-stimulating hormone The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating ho ...
, endothelins,
psoralens Psoralen (also called psoralene) is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered a ...
, hydantoin,
forskolin Forskolin (coleonol) is a labdane diterpene produced by the plant '' Coleus barbatus'' (Blue Spur Flower). Other names include pashanabhedi, Indian coleus, makandi, HL-362, mao hou qiao rui hua. As with other members of the large diterpene class o ...
, cholera toxin,
isobutylmethylxanthine IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine derivatives, is both a: # competitive non-selective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNFα and leukotriene synthesis, and re ...
, diacylglycerol analogues, and UV irradiation all trigger melanogenesis and, in turn, pigmentation. Increased melanin production is seen in conditions where adrenocorticotropic hormone (ACTH) is elevated, such as Addison's and Cushing's disease. This is mainly a consequence of alpha-MSH being secreted along with the hormone associated with reproductive tendencies in primates. Alpha-MSH is a cleavage product of ACTH that has an equal affinity for the MC1 receptor on melanocytes as ACTH. Melanosomes are
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
that package the chemical inside a plasma membrane. The melanosomes are organized as a cap protecting the nucleus of the keratinocyte. When ultraviolet rays penetrate the skin and damage DNA, thymidine dinucleotide (pTpT) fragments from damaged DNA will trigger melanogenesis and cause the melanocyte to produce melanosomes, which are then transferred by dendrites to the top layer of keratinocytes.


Stem cells

The
precursor Precursor or Precursors may refer to: * Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), a hypothesized genus of fossil birds that was composed of fossilized parts of u ...
of the melanocyte is the melanoblast. In adults, stem cells are contained in the bulge area of the
outer root sheath The outer root sheath or external root sheath of the hair follicle encloses the inner root sheath and hair shaft.James, William; Berger, Timothy; Elston, Dirk (2005) ''Andrews' Diseases of the Skin: Clinical Dermatology'' (10th ed.). Saunders. Page ...
of hair follicles. When a hair is lost and the hair follicle regenerates, the stem cells are activated. These stem cells develop into both keratinocyte precursors and melanoblasts - and these melanoblasts supply both hair and skin (moving into the
basal layer The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals. The ''stratum basale'' is a single layer of columnar or ...
of the epidermis). There is additionally evidence that melanocyte stem cells are present in cutaneous nerves, with nerve signals causing these cells to differentiate into melanocytes for the skin.


Clinical significance

* Melanoma - Cancer affecting melanocytes *
Melanocytic tumor Melanocytic tumors are tumors developed from melanocytes. Types * Melanocytic nevus * Melanocytic tumors of uncertain malignant potential * Melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that deve ...
s *
Melanocytic tumors of uncertain malignant potential Melanocytic tumors of uncertain malignant potential (MELTUMP) are melanocytic lesions in the dermis that cannot be classified by morphology as either benign naevi (moles) or malignant melanomas because the mass shows features of both. Several les ...
* Vitiligo - Decreased number of melanocytes due to autoimmune destruction causing decreased melanin * Albinism - Normal number of melanocytes, but decreased melanin production due to decreased tyrosinase activity or defective tyrosine transport * Melasma (Chloasma) - Patchy hyperpigmentation of the skin Normal number of melanocytes with increased melanin production causing hyperpigmentation. Associated with pregnancy or oral contraceptive pill use. *
Addison disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrena ...
* Nevus depigmentosus


See also

* Chromatophore (the pigment
cell type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cell ...
found in poikilotherm animals) * Eye color * Mole (skin marking) * Tanning activator *
List of human cell types derived from the germ layers This is a list of cells in humans derived from the three embryonic germ layers – ectoderm, mesoderm, and endoderm. Cells derived from ectoderm Surface ectoderm Skin * Trichocyte * Keratinocyte Anterior pituitary * Gonadotrope * Corti ...


References


Further reading

* *


External links

* - "Eye: fovea, RPE" * - "Integument: pigmented skin" {{Authority control Human cells Pigment cells Skin anatomy Epithelial cells