Rochin L, Hurbain I, Serneels L, Fort C, Watt B, Leblanc P, Marks MS, De Strooper B, Raposo G, van Niel G.
BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells.
Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10658-63.
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Rochin et al. present convincing data that BACE2, but not BACE1, is involved in pigmentation. Using melanocyte cultures, they found that cleavage of PMEL, an essential step in the formation of melanosome amyloid, requires BACE2. This is interesting because we reported a similar role for presenilins in melanin synthesis and pigmentation (Wang et al., 2006). Our results suggest that trafficking and processing of tyrosinase and related proteins by presenilin/γ-secretase regulate pigmentation. Since γ-secretase substrates first undergo an extracellular/intralumenal cleavage, it would be interesting to see whether BACE2 is responsible for the processing of tyrosinase. The answer will reveal whether BACE2- and presenilin-mediated pigment synthesis are mediated by the same, or distinct, pathways.
Wang R, Tang P, Wang P, Boissy RE, Zheng H.
Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation.
Proc Natl Acad Sci U S A. 2006 Jan 10;103(2):353-8.