Nucleolin is a cell surface receptor of C1QTNF4

C1QTNF4 is a secreted protein that is structurally unique within the C1QTNF family, a family of proteins that have structural homology with both complement C1q and the tumor necrosis factor superfamily. The role of C1QTNF4 in immunity and inflammation remains poorly defined and a cell surface receptor has yet to be identified. Here we performed co-immunoprecipitation with subsequent mass spectrometric analysis in order to identify a cell surface receptor of C1QTNF4. We report identification of nucleolin as a cell surface binding partner of C1QTNF4. Nucleolin may serve as a docking molecule for C1QTNF4 and act in a context-dependent manner through co-receptors. Having identified nucleolin as a cell surface receptor is a further step to understanding C1QTNF4’s function in the healthy immune system.