Cells make enough proteins to perform cell functions and degrade excess or misfolded proteins. They do that through a robust clean-up unit, the proteasome, comprising a pair of proteins 19S and 20S.
Researchers from Max Planck Institute for Brain Research, Germany, found that free-roaming 19S protein particles were adapted to perform crucial additional functions at the synaptic regions of the neuron. In the study published in Science on 25 May, the team found that 19S proteins were influencing the release of neurotransmitters, shedding new light on synapse communication.
“Cells do not like to have extra proteins lying around when they cannot find partners to enable protein function. We call them ‘orphan proteins’. But in this case, it seems like the synapses are making use of these free 19S particles and adapting them to fulfil alternative functions in the synapses,” said Dr Chao Sun lead author, in a statement.
The researchers used a high-resolution imaging technique, DNA PAINT, to tag the proteins with fluorescent markers and observe the happenings at the nanoscale level. According to Dr Sun, 19S not only partnered with 20S but also alone as an independent regulator for key proteins at synapses, revealing a whole new dimension to our understanding of protein function at synapses.
The researchers observed that 19S alters the concentration of an essential glutamate receptor, thereby changing the potency of the transmission of information between neurons.
“AMPA receptors are the main neurotransmitter receptor [for glutamate] for fast synaptic transmission. 19S modifies their ubiquitin (signal for breakdown) signal to maximize the synaptic presence of AMPA receptors, and therefore modulate the efficacy of information transfer at synapses,” Dr Sun told Happiest Health.
Dr Sun adds that in Parkinson’s, a prominent cause is the failure to clear the protein accumulation. As a newly discovered regulator of proteins at these synapses, manipulating the function of 19S may inspire new strategies to facilitate protein clearance at synapses.
“We are expanding our search at synapses, hoping to map the extensive local network of protein regulators that modulate synaptic function. In addition, we plan to study these directly in Parkinson’s disease models,” said Dr Sun.
Dr Chao Sun is currently a group leader at DANDRITE, Aarhus University, Denmark.Â
Read more: Synapse: how neurons communicate
