Melanocytes and their diseases

Abstract

Human melanocytes are distributed not only in the epidermis and in hair follicles but also in mucosa, cochlea (ear), iris (eye), and mesencephalon (brain) among other tissues. Melanocytes, which are derived from the neural crest, are unique in that they produce eu-/pheo-melanin pigments in unique membrane-bound organelles termed melanosomes, which can be divided into four stages depending on their degree of maturation. Pigmentation production is determined by three distinct elements: enzymes involved in melanin synthesis, proteins required for melanosome structure, and proteins required for their trafficking and distribution. Many genes are involved in regulating pigmentation at various levels, and mutations in many of them cause pigmentary disorders, which can be classified into three types: hyperpigmentation (including melasma), hypopigmentation (including oculocutaneous albinism [OCA]), and mixed hyper-/hypopigmentation (including dyschromatosis symmetrica hereditaria). We briefly review vitiligo as a representative of an acquired hypopigmentation disorder.

Figure 1.

Factors that regulate melanin production within melanocytes. Critical factors consist of proteins that affect melanosome structure (Pmel17, MART-1, and GPNMB), proteins that modulate melanin synthesis either directly or indirectly (TYR, TYRP1, DCT, BLOC-1, OA1, P, and SLC45A2), proteins involved in the trafficking of melanosome proteins or the intracellular transport of melanosomes (microtubules, F-actin, kinesin, dynein, Rab27a, melanophilin, myosin Va, RILP, ciliobrevins, and Slp2-a), and melanocyte-specific transcription factors (PAX3, SOX9/10, LEF-1, CREB, DICER, and MITF). Melanosomes mature through distinct stages, noted as I, II, III, and IV in this diagram.

Figure 2.

Diagnosis of congenital hypopigmentation disorders. Key elements for accurate diagnosis are size (systemic or localized), comorbidities, site of the involvement, and patterns/shapes of the lesions.