Upmanyu N, Jin J, Emde HV, Ganzella M, Bösche L, Malviya VN, Zhuleku E, Politi AZ, Ninov M, Silbern I, Leutenegger M, Urlaub H, Riedel D, Preobraschenski J, Milosevic I, Hell SW, Jahn R, Sambandan S
Neuron. 2022 Mar 4:S0896-6273(22)00146-5.
Vesicular transporters (VTs) define the type of neurotransmitter that synaptic vesicles (SVs) store and release. While certain mammalian neurons release multiple transmitters, it is not clear whether the release occurs
from the same or distinct vesicle pools at the synapse. Using quantitative single-vesicle imaging, we show that a vast majority of SVs in the rodent brain contain only one type of VT, indicating specificity for a single
neurotransmitter. Interestingly, SVs containing dual transporters are highly diverse (27 types) but small in proportion (2% of all SVs), excluding the largest pool that carries VGLUT1 and ZnT3 (34%). Using
VGLUT1-ZnT3 SVs, we demonstrate that the transporter colocalization influences the SV content and synaptic quantal size. Thus, the presence of diverse transporters on the same vesicle is bona fide, and depending
on the VT types, this may act to regulate neurotransmitter type, content, and release in space and time.