Proton transfer and substrate recognition in SLC17 transporters

Vesicular glutamate transporters (VGLUTs) accumulate the neurotransmitter glutamate in synaptic vesicles and thus represent an essential determinant of synaptic strength in excitatory synapses in the brain. VGLUTs are modulated by membrane potential and pH and also act as chloride ion channels, thus ensuring their correct functioning during the complete synaptic vesicle cycle. The recent determination of the VGLUT structure, as well as its bacterial homolog DgoT, has opened the way to understand the molecular basis of transport in these two members of the SLC17 family. We aim at investigating the molecular basis of transport by combining computational (classical molecular dynamics, along with massively scalable quantum mechanics/molecular mechanics simulations already used in DynIon’s first period [1]), and experimental approaches (cellular electrophysiology, transport assays and site-directed mutagenesis). Our studies will pave the wave to understand how misregulation of VGLUTs can be implicated in psychiatric and neurodegenerative diseases and potentially develop therapeutic interventions.

[1] Chiariello, M.G., Bolnykh, V., Ippoliti, E., Meloni, S., Olsen, J.M.H., Beck, T., Rothlisberger, U., Fahlke, C., and Carloni, P. (2020)

Molecular Basis of CLC Antiporter Inhibition by Fluoride
J. Am. Chem. Soc. 142, 7254-7258

Integration of multiscale molecular simulations and experimental functional data to understand the molecular basis of transport in vesicular glutamate transporters (VGLUT) and their bacterial homolog (DgoT).

Jun-Prof. Mercedes Alfonso-Prieto

Forschungszentrum Jülich

Institute of Neuroscience and Medicine – Computational Biomedicine (INM-9/IAS-5)

52428 Jülich

Phone: +49 2461 618934

E-mail:

Prof. Dr. Paolo Carloni

Forschungszentrum Jülich

Institute of Neuroscience and Medicine – Computational Biomedicine (INM-9/IAS-5)

52428 Jülich

Phone: +49 2461 618941

E-mail:

Prof. Dr. Christoph Fahlke

Forschungszentrum Jülich

Institute of Biological Information Processing – Molekular- und Zellphysiologie (IBI-1)

52425 Jülich

Phone: +49 2461 614041
E-mail: