The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins.
C1q-like genes (C1ql1-C1ql4) encode small, secreted proteins that are expressed in differential patterns in the brain but whose receptors and functions remain unknown. BAI3 protein, in contrast, is a member of the cell-adhesion class of G protein-coupled receptors that are expressed at high levels in the brain but whose ligands have thus far escaped identification. Using a biochemical approach, we show that all four C1ql proteins bind to the extracellular thrombospondin-repeat domain of BAI3 with high affinity, and that this binding is mediated by the globular C1q domains of the C1ql proteins. Moreover, we demonstrate that addition of submicromolar concentrations of C1ql proteins to cultured neurons causes a significant decrease in synapse density, and that this decrease was prevented by simultaneous addition of the thrombospondin-repeat fragment of BAI3, which binds to C1ql proteins. Our data suggest that C1ql proteins are secreted signaling molecules that bind to BAI3 and act, at least in part, to regulate synapse formation and/or maintenance.
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Marc F
MF
Bolliger
David C
DC
Martinelli
Thomas C
TC
Südhof
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*
C111500:ADGRB3 protein, human; C484729:Adgrb3 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D048069:Tumor Necrosis Factors
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