Compartmentalized distributions of neuronal and glial cell-surface proteins pattern the synaptic network.

Neuronal identity and connectivity are closely linked. Single-cell sequencing studies show that different neuronal cell types express distinct combinations of cell-surface proteins important for synaptic connectivity and function. Emerging evidence indicates that glia-derived cell-surface proteins play critical roles in shaping connectivity as well. These studies begin to suggest that the proteins present on presynaptic and postsynaptic membranes, glial processes, and secreted into the synaptic cleft and extracellular matrix together confer unique surface identities to different types of synaptic connections. Here, we summarize recent findings demonstrating that cell-surface proteins derived from both neurons and glia interact and cooperate to control the connectivity, architecture and function of specific synapses.