They solve the mystery of a protein involved in nervous diseases

Neurotransmission is one of the most complex phenomena in nature and in which a protein machinery must interact precisely and efficiently in just several milliseconds. For this reason, it has always been especially difficult to study in the laboratory.

One of the enigmas was the role of complexin, a protein that is altered in various diseases such as schizophrenia, Alzheimer’s disease or Parkinson’s disease. Until now, some studies showed it as an activator of the release of neurotransmitters, while in other studies and in certain types of synapses the opposite effect was observed. These discrepancies used to be attributed to differences in experimental procedures and/or the species studied, but this has now been found not to be the case.

In a new study, scientists have managed to explain these discrepancies as a consequence of a dual role of complexin.

The study was carried out by a team of researchers from the Max Planck Institute for Multidisciplinary Sciences (MPI-NAT) in Germany, the University of Barcelona (UB) and the Bellvitge Biomedical Research Institute (IDIBELL), located in Hospitalet de Llobregat. and which is one of the institutions CLOSE to the Generalitat of Catalonia.

Thanks to the leadership and previous research of doctors Holger Taschenberger and Kun-Han Lin, and professors Nils Brose and Erwin Neher, the latter winner of the Nobel Prize in Physiology or Medicine in 1991, the research group has used electrophysiology technologies of latest generation to analyze the function of complexin in several central synapses. On the basis of the synaptic responses obtained, a mathematical model has been developed that can reconcile the two apparently contradictory roles of complexin.

Thus, the authors of the study conclude that this protein has a dual function: on the one hand, it acts as a control point ensuring the correct preparation of the vesicles before the nervous stimulus arrives and, on the other, it also promotes the fusion of the vesicles. vesicles during nervous stimulation. Its absence causes the formation of defective vesicles and the aberrant release of neurotransmitters outside of the nervous stimulus, in contrast to a marked release deficit during it.

Dr. Francisco López-Murcia, first author of this study and principal investigator of IDIBELL and the Faculty of Medicine and Health Sciences and the Institute of Neurosciences of the University of Barcelona in this satellite group of the Max-Planck Institute, believes that “over time, this study will be considered a milestone in neurobiology research.”

Dr. Francisco López-Murcia. (Photo: IDIBELL)

A satellite group of the Max-Planck Institute

Dr. López-Murcia has recently joined the cellular and molecular neurobiology research group at IDIBELL and the UB after completing a postdoctoral degree in the laboratory of Professor Nils Brose at the MPI-NAT, in the German city of Göttingen. At least for the next five years, this research group will continue to be linked to the Max Planck Institute as a satellite group, that is, it will have collaboration between researchers and will also receive funding. Thanks to this and his own scholarships, he has already been able to establish the laboratory here from where he can continue researching to “better understand the nervous complications that occur in individuals with mutations in complexin and other synaptic proteins.”

The study is titled “Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion.” And it has been published in the academic journal Proceedings of the Natural Academy of Sciences (PNAS). (Source: IDIBELL)