Recent research has revealed an unexpected independent role for the 19S proteasome particle, traditionally associated with protein degradation, in regulating synaptic proteins at the brain’s synapses. Employing super-resolution imaging through DNA PAINT, scientists discovered that free 19S particles, commonly found in synapses sans their typical partner 20S particles, actively regulate neurotransmitter-related proteins. This discovery suggests that synapses adapt to changing circumstances by utilizing these particles for alternative functions, marking a significant insight into protein versatility within biological systems. Associate Professor Chao Sun, the lead author of the study, highlights that these free 19S particles, often seen as “orphan proteins,” can be repurposed to enhance information transfer and storage at synapses. This finding not only enhances our understanding of synaptic regulation but also opens new avenues for addressing neurological disorders like Parkinson’s disease and dementia, which involve dysfunctional synapses. The study, conducted alongside Erin Schuman at the Max Planck Institute for Brain Research, illuminates the dynamic functionality of the 19S proteasome and its implications for brain health and disease treatment. The article, published in Science, advances the exploration of synaptic adaptation and the role of orphan proteins in cellular biology.
