Abstract
Despite a plethora of information available on the synaptogenesis during development, molecular mechanisms underlying synapse formation and maintenance in adult CNS remain largely unknown. The C1q family is an expanding family consisting of 32 members, such as C1q of the classical complement pathway and adiponectin. We recently demonstrated that Cbln1, a brain-specific C1q family protein, was secreted from cerebellar granule cells and played two crucial roles at granule cell-Purkinje cell synapses: the matching and maintenance of pre- and postsynaptic structures; and the induction of long-term depression, a synaptic plasticity model underlying cerebellar motor learning. Here, we show that Cbln1 is also present outside the cerebellum and other Cbln family proteins Cbln2 and Cbln4 are expressed throughout the CNS with distinct spatial and temporal patterns. In mammalian heterologous cells, Cbln2 and Cbln4 were secreted as N-linked glycoproteins like Cbln1. We found that purified Cbln1, 2, and 4 proteins could bind to distinct postsynaptic regions in the cerebellum and hippocampus. Interestingly, application of exogenous Cbln1 to mature Purkinje cells rapidly increased excitatory synapse formation not only in vitro but also in vivo. These results indicate that Cbln family proteins likely serve as transneuronal regulators of synapse formation and maintenance in distinct brain regions in adult. [J Physiol Sci. 2008;58 Suppl:S6]
