MLANA gene

The MLANA gene (MLANA stands for Melan-A) is a protein-coding gene located on chromosome 9p24.1. Related signaling pathways include NF-kappaB signaling and GPR143 in melanocytes and retinal pigment epithelial cells.

The encoded protein(MART1) can be detected in the membrane of the endoplasmic reticulum, in melanosomes and in the trans-Golgi network.

Diseases associated with MLANA include melanoma in congenital melanocytic nevus and angiomyolipoma.

The MART1 protein is involved in melanosome biogenesis by ensuring the stability of GPR143. It plays an important role in the expression, stability, transport and processing of the melanocyte protein PMEL (seePMEL gene below), which is crucial for the formation of stage II melanosomes.

Human blood monocytes are very efficient in the uptake of antigens. Like tissue macrophages, they efficiently degrade exogenous proteins and are less efficient than dendritic cells (DCs) at cross-presenting antigens to CD8+ T cells. Although it is generally believed that DCs take up tissue antigens and then migrate to the lymph nodes to activate T cells, the mechanisms of presentation of antigens taken up by monocytes are poorly documented. It has been shown that monocytes loaded with long MelanA peptides in vitro retain the ability to stimulate antigen-specific CD8+ T cell clones after 5 days of differentiation into dendritic cells (MoDCs). Labeled long peptides can be visualized in electronically dense endocytic compartments distinct from lysosomes, suggesting that antigens can be protected from degradation over extended periods of time. It has also been demonstrated in blood monocytes from metastatic melanoma patients that in some cases CD14+ monocytes effectively activate a MelanA-specific CD8 T cell clone after in vitro differentiation into MoDCs (Faure F et al. 2018).

1. Faure F et al. (2018) Blood monocytes sample MelanA/MART1 antigen for long-lasting cross-presentation to CD8+ T cells after differentiation into dendritic cells. Int J Cancer 142:133-144.
2. Wandler A et al.(2016) Automated quantification of Ki67/MART1 stains may prevent false-negative melanoma diagnoses. J Cutan Pathol 43:956-962.