Yonamine et al. report that the relative amounts of two sphingolipids control the breakdown of light-sensing proteins and determine whether eye cells survive.
Sphingolipids aren't just building blocks of membranes. Some of the molecules, such as sphingosine 1 phosphate (S1P) and dihydrosphingosine 1 phosphate (DHS1P), take part in signaling pathways that manage everything from heart development to immune cell migration. Yonamine et al. found that these sphingolipids also control endocytosis of rhodopsin and another light-sensitive eye protein, the transient receptor potential (TRP) channel. After exposure to light, receptor cells in the Drosophila eye reduce the levels of these proteins at the membrane. Many of the proteins eventually recycle back to the membrane, but some are diverted to the lysosome for destruction. If too many of these proteins is destroyed, however, photoreceptor cells degenerate.
The researchers found that the balance between recycling and degradation depends on the balance between DHS1P and S1P. When the researchers engineered flies to boost their production of sphingosine kinase 2, which helps synthesize DHS1P, lysosomal destruction of rhodopsin and TRP surged, and large numbers of receptor cells in the animals’ eyes perished. Yonamine et al. saw the same effect if they increased the amount of DHS1P in the animals’ diet. How the ratio between DHS1P and S1P affects cell survival isn't clear, but the researchers suggest that the excessive breakdown of TRP, which normally lets calcium into the cells, dramatically reduces cytosolic calcium levels, causing the cells to die.
