Longield et al_2023_NatComm_Raw

Dataset corresponding to the manuscript "Tau forms synaptic nano-biomolecular condensates controlling the dynamic clustering of recycling synaptic vesicles".
Neuronal communication relies on the release of neurotransmitters from various populations of synaptic vesicles. Despite displaying vastly different release probabilities and mobilities, the reserve and recycling pool of vesicles coexist within a single cluster suggesting that small synaptic biomolecular condensates could regulate the nanoscale distribution. We perform a large-scale activity-dependent phosphoproteome analysis of hipppocampal neurons and identify Tau as a highly phosphorylated and disordered candidate protein. Single-molecule super-resolution microscopy revealed that Tau undergoes LLPS to generate presynaptic nanoclusters whose density and number are regulated by activity. This activiti-dependent diffusion process allows Tau to translocate into the presynapse where forms biomolecular condensates, to selectively control the mobility of recycling vesicles. Tau, therefore, forms presynaptic nano-biomolecular condensates that regulate the nanoscale organization of synaptic vesicles in an activity-dependent manner.