The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins

Abstract

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.

Identification of embryonic stem cell–derived midbrain dopaminergic neurons for engraftment

“…C1ql1, a gene that has been shown to regulate synapse formation (13), was also found to be localized to DA neurons within the adult SN (Supplemental Figure 7C). In terms of cell surface markers, we found that Chrna6 (Table 2), a subunit of the nicotinic acetylcholine receptor (nAChR) that has previously been shown to be expressed in the adult mouse SN (14), was expressed within the developing midbrain in 3 separate mouse databases (ref.…”

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

“…ADGRB1 (BAI1) also binds lipopolysaccharide of Gram-negative bacteria, resulting in Rac signaling and phagocytic uptake (Das et al, 2011). Moreover, ADGRB3 (BAI3) interacts with high affinity with C1q-like molecules and thereby might regulate synapse formation (Bolliger et al, 2011) (Fig. 4F).…”

Shear Stress–Dependent Downregulation of the Adhesion-G Protein–Coupled Receptor CD97 on Circulating Leukocytes upon Contact with Its Ligand CD55

“…CD55 interacts with the N-terminal epidermal growth factor (EGF)-like domains of CD97 (6)(7)(8), an aGPCR broadly expressed by hematopoietic and nonhematopoietic cells (9)(10)(11). Subsequently identified aGPCR ligands were dermatan sulfate, a5b1 integrin, tissue transglutaminase 2, phosphatidylserine, LPS, C1q, lasso/teneurin-2, collagen III, and Thy-1/CD90 (12)(13)(14)(15)(16)(17)(18)(19)(20). Evidence was obtained that aGPCRs have a role in cell positioning and tissue organization in various organ systems (21,22); however, in the strictest sense, aGPCRs are still functional orphans.…”