Trans-Synaptic Interaction of GluRδ2 and Neurexin through Cbln1 Mediates Synapse Formation in the Cerebellum
Copyright policy )Trans-Synaptic Interaction of GluRδ2 and Neurexin through Cbln1 Mediates Synapse Formation in the Cerebellum
Elucidation of molecular mechanisms that regulate synapse formation is required for the understanding of neural wiring, higher brain functions, and mental disorders. Despite the wealth of in vitro information, fundamental questions about how glutamatergic synapses are formed in the mammalian brain remain unanswered. Glutamate receptor (GluR) delta2 is essential for cerebellar synapse formation in vivo. Here, we show that the N-terminal domain (NTD) of GluRdelta2 interacts with presynaptic neurexins (NRXNs) through cerebellin 1 precursor protein (Cbln1). The synaptogenic activity of GluRdelta2 is abolished in cerebellar primary cultures from Cbln1 knockout mice and is restored by recombinant Cbln1. Knockdown of NRXNs in cerebellar granule cells also hinders the synaptogenic activity of GluRdelta2. Both the NTD of GluRdelta2 and the extracellular domain of NRXN1beta suppressed the synaptogenic activity of Cbln1 in cerebellar primary cultures and in vivo. These results suggest that GluRdelta2 mediates cerebellar synapse formation by interacting with presynaptic NRXNs through Cbln1.
- University of Edinburgh United Kingdom
- Niigata University Japan
- University of Tokyo Japan
PROTEINS, Biochemistry, Genetics and Molecular Biology(all), Receptors, Glutamate/metabolism, Calcium-Binding Proteins, Nerve Tissue Proteins/metabolism, Nerve Tissue Proteins, Protein Precursors/metabolism, MOLNEURO, Cell Line, /dk/atira/pure/subjectarea/asjc/1300, Mice, Receptors, Glutamate, Cerebellum, Synapses, Animals, Humans, Neural Cell Adhesion Molecules/metabolism, Protein Precursors, Neural Cell Adhesion Molecules, Cells, Cultured, Cerebellum/metabolism
PROTEINS, Biochemistry, Genetics and Molecular Biology(all), Receptors, Glutamate/metabolism, Calcium-Binding Proteins, Nerve Tissue Proteins/metabolism, Nerve Tissue Proteins, Protein Precursors/metabolism, MOLNEURO, Cell Line, /dk/atira/pure/subjectarea/asjc/1300, Mice, Receptors, Glutamate, Cerebellum, Synapses, Animals, Humans, Neural Cell Adhesion Molecules/metabolism, Protein Precursors, Neural Cell Adhesion Molecules, Cells, Cultured, Cerebellum/metabolism
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