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. |