Orphan No More

Science Signaling  20 Apr 2010:
Vol. 3, Issue 118, pp. ec118
DOI: 10.1126/scisignal.3118ec118

The glutamate receptor δ2 (GluD2), another member of the ionotropic glutamate receptor family, has long been considered to be an orphan receptor because there are no known endogenous ligands. Nevertheless, GluD2 is essential for the normal development of cerebellar circuits. Using immunocytochemistry, binding assays, electrophysiology, and freeze-fracture electron microscopy, Matsuda et al. found that Cbln1, a soluble protein secreted from cerebellar granule cells, binds to the extracellular N terminus of GluD2 on Purkinje cells. Binding has two independent consequences: First, it leads to presynaptic differentiation; second, it causes postsynaptic clustering of several important synapse-specific molecules. Both events are needed for synapse formation between granule cells and Purkinje cells.

K. Matsuda, E. Miura, T. Miyazaki, W. Kakegawa, K. Emi, S. Narumi, Y. Fukazawa, A. Ito-Ishida, T. Kondo, R. Shigemoto, M. Watanabe, M. Yuzaki, Cbln1 is a ligand for an orphan glutamate receptor δ2, a bidirectional synapse organizer. Science 328, 363–368 (2010). [Abstract] [Full Text]