A human IgSF cell-surface interactome reveals a complex network of protein-protein interactions

Cell-surface protein-protein interactions (PPIs) mediate cell-cell
communication, recognition and responses. We executed an interactome
screen of 564 human cell-surface and secreted proteins, most of which are
immunoglobulin superfamily (IgSF) proteins, using a high-throughput,
automated ELISA-based screening platform employing a pooled-protein
strategy to test all 318,096 PPI combinations. Screen results, augmented
by phylogenetic homology analysis, revealed ~380 previously unreported
PPIs. We validated a subset using surface plasmon resonance and cell
binding assays. Observed PPIs reveal a large and complex network of
interactions both within and across biological systems. We identified new
PPIs for receptors with well-characterized ligands, and binding partners
for ‘orphan’ receptors. New PPIs include proteins expressed on multiple
cell types, and involved in diverse processes including immune and nervous
system development and function, differentiation/proliferation,
metabolism, vascularization, and reproduction. These PPIs provide a
resource for further biological investigation into their functional
relevance, and may offer new therapeutic drug targets.