Scientists resolve the hitherto controversially discussed function of complexin in synapses

This study proposes a model that reconciles seemingly contradictory observations regarding the synaptic function of complexin, a protein also involved in certain nervous diseases.

Researchers from IDIBELL, the UB and the Max Planck Institute for Multidisciplinary Sciences collaborate thanks to the formation of a satellite group.

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Sciences collaborate thanks to the formation of a satellite group.

Neurotransmission is one of the most complex processes in nature. It is governed by a precisely and efficiently interacting protein machinery. Because of its temporal and spatial precision, it is particularly challenging to study this process in the laboratory. One of its conundrums was the role of complexin, a protein found in virtually all nerve endings. The abundance of complexin can be altered in various disease contexts such as schizophrenia, Alzheimer’s or Parkinson’s. While complexin loss generally weakens synapses, some studies also ascribed complexin the role of a suppressor of spontaneous neurotransmitter release, preventing a “premature” fusion of synaptic vesicles, while no evidence for such role was found in other experiments. Such discrepancies were attributed to different experimental procedures and/or species used, but this has now been refuted.

A study recently published in PNAS by researchers from IDIBELL, UB and the Max-Planck Institute of Multidisciplinary Sciences (MPI-NAT) proposes a new role for complexin with the potential to reconcile these discrepancies. Thanks to the leadership and previous research of Drs. H. Taschenberger and K.-H. Lin, and Profs. N. Brose and E. Neher, the latter a Nobel Prize in Physiology or Medicine winner in 1991, the research group was able to combine genetic mouse models with state-of-the-art electrophysiology techniques to analyze complexin’s function in several brain synapses. Based on the observed synaptic responses in the presence or absence of complexin expression, they developed a mathematical model that can reproduce contrasting effects of complexin ablation on neurotransmission in different synapses. The team proposes a dual function for the protein: on the one hand, it acts as a control point ensuring a correct preparation of synaptic vesicles for subsequent rounds of synaptic vesicle fusion, and, on the other hand, it also promotes vesicle fusion during a nerve stimulus. Absence of complexin causes the formation of a malfunctioning protein machinery which leads to an aberrant increase of delayed neurotransmitter release, contrasting the dramatic reduction in release immediately triggered by a nerve impulse.

Dr. Francisco López-Murcia, first author of this study and principal investigator at IDIBELL and UB in this Max-Planck Institute satellite group, firmly believes that “in time, this article will be considered a milestone in neurobiology research”.

A satellite group of the Max-Planck Institute

Dr López-Murcia has recently joined the IDIBELL and UB cellular and molecular neurobiology research group after completing his postdoctorate in Prof. Nils Brose lab at the MPI-NAT, in 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 to say, the researchers will collaborate and will also receive funding from MPI. Thanks to this and his own grants, he has already established his new laboratory to continue his research to “achieve a better understanding of the nervous complications shown by individuals with mutations in complexin and other synaptic proteins”.





The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).

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