New Insights Into Mechanism of Protein Sorting and Its Disfunction in Synapses

The senior author of the study Joris de Wit (left) and the first author Jeffrey Savas (right). Image: The Flanders Institute for Biotechnology (VIB).

Leuven, Belguim (Scicasts) — Genetic analysis of human patients has shown that mutations in genes involved in synaptic communication can drive neuropsychiatric and neurological diseases such as autism spectrum disorder and Alzheimer’s disease.

Through a global analysis of the synaptic machinery Jeffrey Savas and Joris de Wit together with their colleagues revealed for the first time a new pathway that governs the proper sorting of many essential synaptic proteins in neurons.

“Jeff and I started this work in the US, when Jeff was a postdoc with John R. Yates III at The Scripps Research Institute and I was a postdoc with Anirvan Ghosh at the University of California San Diego,” says Joris de Wit, a group leader at the Flanders Institute of Biotechnology in Leuven.

“We continued this work after we both established our own labs, with the help of Luís Ribeiro here at VIB/KU Leuven. This intense international collaboration has enabled us to use cutting-edge proteomic technology to study the entire synaptic machinery rather than individual elements.”

Novel technologies such as high-content protein analysis allowed scientists to study synapses on a global level and identify a master regulator in the process of synaptic proteins sorting, receptor SorCS1.

Experiments showed that disruption of this pathway impedes efficient communication between neurons. Mutations in this sorting pathway have previously been found in several synaptic diseases, including autism spectrum disorder and Alzheimer’s disease.

The results show that perturbed sorting of these synaptic proteins hampers neuron-neuron communication and culminates in an increased level of silent synapses, explains de Wit.

“Our work highlights the importance of proper synaptic protein sorting for efficient neuronal communication and suggests that therapeutic targeting of this pathway could prove beneficial to improve synaptic function in brain disorders,” he says.

Article adapted from a Flanders Institute of Biotechnology (VIB) news release.

Publication: The Sorting Receptor SorCS1 Regulates Trafficking of Neurexin and AMPA Receptors. Savas, JN et al. Neuron (August 19, 2015): Click here to view

Source: New Insights Into Mechanism of Protein Sorting and Its Disfunction in Synapses

Via: Google Alert for Neuroscience