Understanding synaptic proteins and the brain

Dr Davide Comoletti from the School of Biological Sciences has completed a cross-institutional project with interesting biological implications for the neuroscience and structural biology communities.

Alongside researchers from Victoria University of Wellington, The State University of New Jersey, the University of Lethbridge, and the University of Chicago, including undergraduate and postgraduate students, postdoctoral researchers, and research staff, Dr Comoletti investigated interactions between proteins that are critical for the formation and maintenance of synapses between neurons.

“The identity of these proteins is known, but their network of interactions has so far remained obscure,” Dr Comoletti says. “We have identified 200 interactions between the proteins and determined the three-dimensional structure of three IgLONS, a family of five proteins of the immunoglobin superfamily that has recently been implicated in a wide range of human diseases.”

Of the protein interactions discovered by Dr Comoletti and his colleagues, 89 of them were previously unpublished. In addition to the crystal structures, they were also able to describe how the IgLONS make two cells interact and found that the size of the protein fits perfectly in the narrow space between two neurons, consistent with their roles in synapses.

“The sheer number of interactions and the number of novel interactions we discovered was very unexpected, because identifying protein interactions typically takes years of work,” Dr Comoletti says.

Dr Comoletti says they have also been able to demonstrate that many proteins have not just one receptor, but multiple receptors, a finding he says will be of interest to molecular neuroscientists, proteomics experts, and structural biologists.

Dr Comoletti and his colleagues plan to build on this research by studying these new interactions between proteins that have medical relevance, such as the IgLONs or Reelin, which is a protein implicated in autism and schizophrenia, Dr Comoletti says.

This publication is the result of initial work funded by the US National Science Foundation as part of the BRAIN initiative started by President Obama. The BRAIN Initiative aims to improve understanding of the brain and how we treat, prevent, and cure brain disorders.