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Pigmentation Research

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Pigmentation is the darkening of the skin due to an excess of melanin, which is the body's natural pigment. Pigmentation can occur in any part of the body but is most common on the face, neck, and hands. Pigmentation can be caused by various factors, including sun exposure, hormones, and certain medical conditions. Pigmentation research is essential to develop new and more effective treatments for these disorders.

A graphic demonstration of skin discoloration types.Fig.1 A graphic demonstration of skin discoloration types. (Avcil, et al., 2020)

Membrane Proteins Associated with Pigmentation

  • Ion Transport Proteins

Ion transporters, including ion channels, ion pumps, and ion transporters, play important roles in various cellular activities at the plasma membrane and intracellular organelles. The function of transporters depends on electrochemical gradients. Channels selectively facilitate passive diffusion. Active transport systems move these species against their electrochemical gradients. Maintenance of ion homeostasis requires combined functions of ion transporters. In melanosomes, ions are integral to the nature of organelles that determine melanogenesis and biogenesis. Ions and their transporters contribute to enzymatic reactions, redox reactions, electrical signaling, metal and ion homeostasis, and pH maintenance.

  • Membrane Proteins Specific to Melanosomes

Consistent with their tissue-specific function, melanosomes harbor numerous tissue-specific proteins that function as enzymes, structural scaffolds, and/or ion channels to optimize the synthesis, polymerization and detoxification of melanin intermediates. Some of the main melanosome membrane components include:

    • TYRP1 - a tyrosinase-related protein that may catalyze or modulate tyrosinase activity; it is found at a steady state predominantly in stage III and IV melanosomes.
    • PMEL17 - a structure composed of the melanosome fibrillar 'matrix' on which melanins are deposited; it accumulates in stage I and II melanosomes and is masked by melanin in later stages.
    • MART1 - a small integral membrane protein. It regulates fibril formation by PMEL17 and is present in melanosomes and late endosomes.
    • OA1 - a putative G-protein-coupled receptor that is found on melanosomes and lysosomes.
    • OCA2 - a putative anion transporter that is likely to be present in melanosomes.
    • SLC45A2 - a putative membrane transporter that is likely to be present in melanosomes.
    • SLC24A5 - a putative cation exchanger that is likely to be present in melanosomes.

Model of delivery of selected cargoes to late-stage melanosomes.Fig.2 Model of delivery of selected cargoes to late-stage melanosomes. (Sitaram & Marks, 2012)

References

  1. Avcil, M.; et al. Clinical efficacy of dissolvable microneedles armed with anti-melanogenic compounds to counter hyperpigmentation. Journal of Cosmetic Dermatology. 2021, 20(2): 605-614.
  2. Sitaram, A.; Marks, M. Mechanisms of protein delivery to melanosomes in pigment cells. Physiology. 2012, 27(2): 85-99.

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