| First Author | Chen J | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 2 | Pages | 512-25 |
| PubMed ID | 21228161 | Mgi Jnum | J:168230 |
| Mgi Id | MGI:4887488 | Doi | 10.1523/JNEUROSCI.3771-10.2011 |
| Citation | Chen J, et al. (2011) Calcium channels link the muscle-derived synapse organizer laminin beta2 to bassoon and CAST/Erc2 to organize presynaptic active zones. J Neurosci 31(2):512-25 |
| abstractText | Synapse formation requires the organization of presynaptic active zones, the synaptic vesicle release sites, in precise apposition to postsynaptic neurotransmitter receptor clusters; however, the molecular mechanisms responsible for these processes remain unclear. Here, we show that P/Q-type and N-type voltage-dependent calcium channels (VDCCs) play essential roles as scaffolding proteins in the organization of presynaptic active zones. The neuromuscular junction of double knock-out mice for P/Q- and N-type VDCCs displayed a normal size but had significantly reduced numbers of active zones and docked vesicles and featured an attenuation of the active-zone proteins Bassoon, Piccolo, and CAST/Erc2. Consistent with this phenotype, direct interactions of the VDCC beta1b or beta4 subunits and the active zone-specific proteins Bassoon or CAST/Erc2 were confirmed by immunoprecipitation. A decrease in the number of active zones caused by a loss of presynaptic VDCCs resembled the pathological conditions observed in the autoimmune neuromuscular disorder Lambert-Eaton myasthenic syndrome. At the synaptic cleft of double knock-out mice, we also observed a decrease of the synaptic organizer laminin beta2 protein, an extracellular ligand of P/Q- and N-type VDCCs. However, the transcription level of laminin beta2 did not decrease in double knock-out mice, suggesting that the synaptic accumulation of laminin beta2 protein required its interaction with presynaptic VDCCs. These results suggest that presynaptic VDCCs link the target-derived synapse organizer laminin beta2 to active-zone proteins and function as scaffolding proteins to anchor active-zone proteins to the presynaptic membrane. |
