The novel factor Active Breakpoint Cluster Region-Related Protein (ABR) contributes to melanocyte migration

Motonori Kurosumi, Maiko Yamada, Yoshihiro Hamanaka, Chihiro Kondo, Shoko Sassa
POLA Chemical Industries, Inc., Yokohama, Japan

It has been reported that skin pigmentation is caused by overproduction of melanin as a result of melanocyte activation. Besides, melanin distribution is known to important factor for forming skin pigmentation. Vertical distribution of melanin is regulated by controlling epidermal turnover. On the other hand, controlling mechanisms of horizontal melanin distribution still remain unclear.
In the process of wound closure, melanocyte is known to have an ability to migrate into wound site from marginal region, especially from hair bulge. However, in normal skin condition, melanocyte seems to be retaining on basement membrane despite that melanocytes are densified in pigmented sites according to clinical findings. Therefore, we hypothesized that overcrowding of melanocytes would be involved in skin pigmentation. The purpose of this study is to clarify the factors influencing the mechanism of skin pigmentation focusing on melanocyte distribution.
We confirmed that the overcrowding condition during culturing melanocytes increases melanin production per cell. Since melanocytes differentiate directly from neural crest cells same as neural cells, we focused on Active Breakpoint Cluster Region-Related Protein (ABR) which is known to be a factor involved in cellular dynamics of neurons. As a result of analyzing the gene function, ABR knocked-down melanocyte enhanced cell migration and decrease melanocytes densities. Furthermore, ABR knocked-down melanocyte decreased melanin production. From the results of the microarray, ABR was confirmed to be involved in the expression of Rho family such as Rac1. These results indicated the possibility of ABR controlling cellular dynamics especially cell polarity and cytoskeletal remodeling. It was suggested that ABR induces melanocyte congestion by suppressing cell polarity regulatory factors and ABR could be novel factor controlling skin pigmentation.