Misfolded prion protein causes the buildup of voltage-gated calcium channels inside the cell, interfering with normal neuronal communication and causing motor dysfunction, according to a recent study (Neuron 74, 300–313).

Mutations in the PRNP gene can lead to PrP protein aggregation and can cause a variety of neurological diseases in humans that are commonly linked to motor dysfunction. Assunta Senatore et al. found that, compared with mice expressing wild-type PrP, mice expressing mutant PrP showed reductions in glutamate release at synapses in the cerebellum, a part of the brain that controls motor function.

Voltage-gated calcium channels (VGCCs) are required at the surface of synapses for normal release of glutamate. The researchers found that mutant PrP bound VGCCs and prevented them from being delivered to the cell surface. These findings suggest that enhancing VGCC transport to synapses could ameliorate motor dysfunction in prion diseases.