Dopamine transmission is involved in reward processing and motor control, and its impairment plays a central role in numerous neurological disorders. Despite its strong pathophysiological relevance, the molecular and structural organization of the dopaminergic synapse remains to be established. We used targeted labeling and fluorescence-activated sorting to purify striatal dopaminergic synaptosomes. Our data reveal the adhesion of dopaminergic varicosities to glutamatergic, GABAergic, or cholinergic synapses in tripartite structures we named “dopamine hub synapses.” We provide the proteome of dopaminergic hub synapses with 57 proteins specifically enriched compared to bulk striatal synaptosomes. Among a handful of undocumented candidates, SynCAM 2, a ubiquitous synaptic adhesion molecule, is particularly enriched in dopaminergic varicosities engaged at dopamine hub synapses. We show that glutamatergic synapses, display a molecular remodeling of pre- and postsynaptic markers when associated with a dopamine hub synapse. In the present work we investigate the role of SYNCAM 2 in the formation and maintenance of dopamine hub synapses. Preliminary data supports a function of SynCAM 2 in a trans-synaptic signaling and plasticity. Our work raises the question of the respective contributions of synaptic versus volume transmission of dopamine to modulate network activity.