Lafora disease is a fatal form of epilepsy whose symptoms usually begin between the ages of 10 and 20. In neurodegenerative diseases such as Parkinson's and Alzheimer's, globs of insoluble proteins amass in neurons. But in Lafora disease, neurons harbor clumps of insoluble carbohydrates similar to amylopectin, a component of starch. Several mutations can trigger the illness, including glitches in the gene for laforin. This protein carries two key modules: one that grabs carbohydrates, and a second that slices off phosphate groups. Although mouse models develop the symptoms of Lafora disease, researchers still don't understand how their faulty laforin protein elicits neurological damage.
Gentry et al. thus went hunting for other laforin-making organisms. They trolled protist genomes and pinpointed genes for laforin in organisms as different as the pathogen behind toxoplasmosis and a type of red alga. Previously, researchers had thought that only vertebrates manufacture the protein. Like human laforin, the protist version grips carbohydrates and lops off a phosphate. Where laforin hangs out has been a mystery, but the researchers determined that, in one type of protist, it congregates around starch granules.
The team also found that plants carry an unrelated protein with the same function, known as SEX4. Arabidopsis plants with a defective form of SEX4 built up excess starch. The presence of proteins with the same job in such a range of organisms suggests that phosphate removal is crucial for breaking down insoluble carbohydrates. Why persistent phosphates lead to carbohydrate buildup remains unclear. The scientists now want to investigate whether the carb clusters from patients with Lafora disease carry excess phosphates.