Surfaceome dynamics and surface trafficking during neuronal development and synaptic plasticity

Surface proteins are of fundamental importance for formation of synaptic connections and activity-dependent plasticity. Here, we used a spatiotemporally resolved cell-surface proteotype analysis to characterize the neuronal surface-exposed proteome, or surfaceome, during neuronal development and synapse formation in primary neuronal cultures. We established a map of the neuronal surfaceome, which includes about 1,000 surface proteins, and analyzed the dynamic remodeling of the quantitative surfaceome during development. We identified time-resolved surface-abundance profile clusters that correspond to distinct stages of neuronal development. We discovered that surface abundance changes can correlate with or be uncoupled from the total cellular abundance. Finally, we observed system-wide surfaceome modulation in response to homeostatic synaptic scaling and exocytosis of diverse cargo during long-term potentiation.