| First Author | Matsuda K | Year | 2011 |
| Journal | Eur J Neurosci | Volume | 33 |
| Issue | 8 | Pages | 1447-61 |
| PubMed ID | 21410790 | Mgi Jnum | J:177327 |
| Mgi Id | MGI:5294741 | Doi | 10.1111/j.1460-9568.2011.07638.x |
| Citation | Matsuda K, et al. (2011) Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. Eur J Neurosci 33(8):1447-61 |
| abstractText | Cbln1 (a.k.a. precerebellin) is a unique bidirectional synaptic organizer that plays an essential role in the formation and maintenance of excitatory synapses between granule cells and Purkinje cells in the mouse cerebellum. Cbln1 secreted from cerebellar granule cells directly induces presynaptic differentiation and indirectly serves as a postsynaptic organizer by binding to its receptor, the delta2 glutamate receptor. However, it remains unclear how Cbln1 binds to the presynaptic sites and interacts with other synaptic organizers. Furthermore, although Cbln1 and its family members Cbln2 and Cbln4 are expressed in brain regions other than the cerebellum, it is unknown whether they regulate synapse formation in these brain regions. In this study, we showed that Cbln1 and Cbln2, but not Cbln4, specifically bound to its presynaptic receptor -alpha and beta isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] - and induced synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. Cbln1 competed with synaptogenesis mediated by neuroligin 1, which lacks the splice sites A and B, but not leucine-rich repeat transmembrane protein 2, possibly by sharing the presynaptic receptor NRXs(S4+). However, unlike neurexins/neuroligins or neurexins/leucine-rich repeat transmembrane proteins, the interaction between NRX1beta(S4+) and Cbln1 was insensitive to extracellular Ca(2+) concentrations. These findings revealed the unique and general roles of Cbln family proteins in mediating the formation and maintenance of synapses not only in the cerebellum but also in various other brain regions. |
