Alpha‐Synuclein Promotes Anterograde Vesicle Transport in Melanocytes and Melanoma Cells: A Pro‐Survival Function

ABSTRACT A great scientific achievement has been the elucidation of the role that the presynaptic protein α‐synuclein (α‐syn) plays in Parkinson's disease (PD). α‐syn has a propensity to aggregate into a myriad of soluble and insoluble states, some of which are cytotoxic and that trigger the degeneration of dopaminergic neurons in the mid‐brain. Although highly expressed in neurons, α‐syn is also expressed in skin, specifically melanocytes, and is robustly expressed in primary and metastatic melanomas. Epidemiological studies have identified a co‐occurrence of melanoma and PD, in that, compared to healthy individuals, melanoma patients have a significantly higher risk of developing PD, and PD patients have a significantly higher risk of developing melanoma. Such a co‐occurrence indicates that shared pathogenic triggers may underlie both diseases. Although there is no definitive evidence that α‐syn is the pathogenic trigger, my interest has been to decipher the function of α‐syn in melanoma. Herein, I give a background on melanoma biology, α‐syn structure and function, pigment production in neurons and melanocytes, and then focus on evidence that α‐syn promotes melanoma proliferation and progression by facilitating the intracellular transport of key proteins, which support invasion and migration, to the plasma membrane.