Neighbors control trafficking

Abstract

Neuron-derived signals induce myelination by oligodendrocytes. On page 937, Trajkovic et al. report that neurons achieve this goal, in part, by triggering exocytosis of myelin membrane proteins from late endosomes or lysosomes to the plasma membrane. Proteolipid protein (PLP) is a major component of the myelin membrane sheath that surrounds axons. The team found that although PLP was initially transported to the plasma membrane of immature oligodendrocytes, it was efficiently endocytosed in a clathrin-independent manner and stored in late endosomes or lysosomes (LE/L). When oligodendrocytes were cocultured with neurons, however, PLP localization in the LE/L was decreased. Retrograde vesicle movement increased, and the PLP was exocytosed and dumped into the myelin membrane. It is not yet clear what the signal from neurons is that triggers PLP exocytosis, but the signaling cascade required cAMP signaling within the glial cell. Moreover, direct cell contact between the neuron and oligodendrocyte was not required, implying that the signaling factor is secreted by the neurons and is soluble. The team is currently trying to identify the signal using a two-pronged approach: systematic screening in case it is a novel factor; and testing previously identified neuron–glia signaling molecules. So far they have not found a signal that triggers PLP movement. But the current work establishes that one cell type can influence membrane trafficking in a neighboring cell type—and thus that studying vesicle transport in single-cell cultures may reveal only a portion of the picture.