Melanin's backups

Sports teams and melanin-making cells follow the same strategy: they have substitutes in case a regular can't perform. The cells rely on redundant proteins to deliver enzymes for pigment production, as Wasmeier et al. report on page 271. The results might clarify researchers' understanding of an enigmatic class of cell organelles that participate in everything from immunity to blood clotting.

The melanosomes that manufacture melanin are lysosome-related organelles (LROs), which store and synthesize molecules in many cell types. In platelets, for example, LROs house coagulation factors. Researchers are still working out the details of LRO formation. One mystery is how melanosomes stock up on the enzymes tyrosinase and tyrosinase-related protein-1 (Tyrp1), which are essential for making melanin. Wasmeier et al. investigated one protein that might have a role in the process, Rab38.

Mice with a faulty version of Rab38 are less dark than usual, but they are not albinos, suggesting that another protein picks up the pigmentation slack. The team identified the backup as Rab38's relative, Rab32. Cells lacking both proteins are pale, and their melanosomes show scant tyrosinase and Tyrp1.

The researchers tracked Rab38 and Rab32 to vesicles that often harbored tyrosinase or Tyrp1. Wasmeier et al. conclude that the two proteins somehow help pick up freshly minted enzymes from the Golgi apparatus and bundle them into endosomes for shipment to the melanosomes. How Rab38 and Rab32 work together and whether they help fashion other LROs remain open questions.