Cbln1 and its family proteins in synapse formation and maintenance

Cbln1 is a newly identified synaptic organizer belonging to the C1q family. Unlike other synaptic organizers, a deficiency in Cbln1 is sufficient to cause a severe reduction in the number of synapses between cerebellar Purkinje cells and parallel fibers (PFs). Furthermore, Cbln1 can rapidly induce synaptogenesis and is necessary for maintaining normal synapses in the mature cerebellum in vivo. Cbln1 was recently identified as the missing ligand for the orphan glutamate receptor δ2 (GluD2), which is expressed in Purkinje cells. Furthermore, Cbln1 released from PFs binds to neurexin (NRX) expressed on the presynaptic PFs and GluD2 at the postsynaptic site. The NRX/Cbln1/GluD2 tripartite complex is resistant to low extracellular Ca2+ levels and serves as a unique bidirectional synaptic organizer.

Research highlights► Cbln1 is indispensable for synapse formation and maintenance in the cerebellum. ► Cbln1 binds to neurexin and GluD2 at the presynaptic and postsynaptic sites, respectively. ► This tripartite complex is a unique bidirectional synaptic organizer. ► Each component of the tripartite complex is regulated by neuronal activity. ► Cbln1, Cbln2, and GluD1 likely regulate synaptic functions outside the cerebellum.