Axonal transport and active zone proteins regulate dopaminergic synapse formation

At a typical synapse, the precise juxtaposition between the active zone and postsynaptic receptors ensures local and precise neurotransmitter release and detection. Dopamine neurons release neurotransmitter more diffusely using volume-transmission, where precise pre- and post-synaptic alignment is lacking. It is unknown whether Dopaminergic presynaptic terminals have typical active zone structures and how they develop. Here we show that presynaptic terminals of the C. elegans dopaminergic neuron PDE contain bona fide AZ proteins, including SYD-2/Liprin-, ELKS-1, UNC-10/RIM and CLA-1/Piccolo. During development, synaptic vesicles (SVs) and active zone proteins (AZs) coalesce within minutes behind the advancing growth cone. Precise regulation of UNC-104/Kinesin-3-mediated SV transport through kinesin autoinhibition is required to pause transported SVs at synapses. SYD-1 and SYD-2 recruit and cluster the transiting SVs, while ELKS-1 aggregates through a distinct mechanism.