Some human diseases occur episodically in people who appear otherwise healthy. One of these disorders is paroxysmal nonkinesigenic dyskinesia (PNKD). The neurological disease’s symptoms – involuntary movements in the limbs, torso, and face – are triggered by coffee, alcohol, and stress. In 2004, HHMI Investigator Louis J. Ptáček at the University of California, San Francisco, discovered the gene that causes PNKD. Now, just over a decade later, he’s figured out what the gene does.
To deduce the function of the PNKD gene, Ptáček’s team raised antibodies against the PNKD protein. This allowed them to isolate PNKD and its binding partners from mouse brain tissue. From these isolates, they discovered that PNKD interacts with two other proteins, called RIM1 and RIM2, that are involved in neurotransmitter release. As the scientists reported March 10, 2015, in the Proceedings of the National Academy of Sciences, PNKD normally suppresses neurotransmitter release, but the mutant form found in the disease does so less effectively. The result is excessive synaptic transmission, which leads to the involuntary movements experienced by people with the disease.
According to Ptáček, RIM1 and RIM2 may be important targets for developing better medications for PNKD and other dyskinesias, such as those seen in Parkinson’s disease.