Seminar: Zohreh Farsi, theme Cancer development and immunce defence

How neurotransmitters are loaded in synaptic vesicles

10 March 2016 12:00 hrs. - 13:00 hrs.
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
How neurotransmitters are loaded in synaptic vesicles

Zohreh Farsi, Max Planck Institute of Biophysical Chemistry, Dept. of Neurobiology, Göttingen, Germany


Geert van den Bogaart, Dept. of Tumor Immunology, Radboudumc

10-03-2016 12:00:0010-03-2016 13:00:00Europe/AmsterdamHow neurotransmitters are loaded in synaptic vesicles Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route

Remarks / more information:

undefinedundefinedIn order to maintain high-fidelity synaptic transmission, a single synaptic vesicle (SV) must load more than 2,000 neurotransmitter molecules in each round of SV recycling. Vesicle filling requires generation of an electrochemical proton gradient (∆µH+), which is composed of a chemical (∆pH) and an electrical (∆ψ) component, to fuel the vesicular transporters. It is evident that contribution of ∆pH and ∆ψ to uptake of distinct neurotransmitters is different due to the difference in their net charge. However, it is not clear how large amount of either of these transmitters can be accumulated within the few seconds of SV recycling, while maintaining a strict balance of charge and osmolarity during their transport. Existing models so far have been proposing that uptake of these transmitters are probably associated with the compensating ion fluxes which are either mediated by the transporter itself or provided by other ion exchangers present on SVs. However, there are still major disagreements. Moreover, whether these compensating mechanisms are different in glutamatergic and GABAergic vesicles, and if this is the case, the molecular mechanisms underlying these differences are still enigmatic, particularly when considering that these vesicles have a nearly identical molecular composition.  Using single-vesicle imaging to measure both components of ∆µH+,we now directly show different uptake mechanisms in glutamatergic and GABAergic SVs operating in parallel. In contrast to glutamate, uptake of GABA is coupled to proton efflux, with no other ions participating in the transport cycle. Furthermore, we provide evidence that there are significant differences in regulation of ∆µH+ between glutamatergic and GABAergic SVs and vesicular transporters are the responsible molecules for these differences. In addition to their primary critical roles as neurotransmitter transporters, this adds yet another level of complexity to the contribution of vesicular transporters to maintenance of fidelity in synaptic transmission.

Key publication:

  • Z Farsi, J Preobraschenski, G van den Bogaart, D Riedel, R Jahn & A Woehler. (2016) Single-vesicle imaging reveals different transport mechanisms between glutamatergic and GABAergic vesicles. Science. In press.

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