Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing Export

@article{citeulike:4380795, abstract = {10.1073/pnas.0813112106 Synapse formation at the neuromuscular junction (NMJ) requires an alternatively spliced variant of agrin (Z agrin) that is produced only by neurons. Here, we show that Nova1 and Nova2, neuron-specific splicing factors identified as targets in autoimmune motor disease, are essential regulators of Z agrin. / double knockout mice are paralyzed and fail to cluster AChRs at the NMJ, and breeding them with transgenic mice constitutively expressing Z agrin in motor neurons rescued AChR clustering. Surprisingly, however, these rescued mice remained paralyzed, while electrophysiologic studies demonstrated that the motor axon and synapse were functional-spontaneous and evoked recordings revealed synaptic transmission and muscle contraction. These results point to a proximal defect in motor neuron firing in the absence of Nova and reveal a previously unsuspected role for RNA regulation in the physiologic activation of motor neurons.}, author = {Ruggiu, Matteo and Herbst, Ruth and Kim, Natalie and Jevsek, Marko and Fak, John J. and Mann, Mary A. and Fischbach, Gerald and Burden, Steven J. and Darnell, Robert B.}, citeulike-article-id = {4380795}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0813112106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/9/3513.long.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/9/3513.long.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19221030}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19221030}, day = {3}, doi = {10.1073/pnas.0813112106}, journal = {Proceedings of the National Academy of Sciences}, keywords = {agrin}, month = {March}, number = {9}, pages = {3513--3518}, posted-at = {2009-04-22 22:44:36}, priority = {2}, title = {Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing}, url = {http://dx.doi.org/10.1073/pnas.0813112106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4380795 L3 - citeulike-article-id:4380795 N2 - 10.1073/pnas.0813112106 Synapse formation at the neuromuscular junction (NMJ) requires an alternatively spliced variant of agrin (Z agrin) that is produced only by neurons. Here, we show that Nova1 and Nova2, neuron-specific splicing factors identified as targets in autoimmune motor disease, are essential regulators of Z agrin. / double knockout mice are paralyzed and fail to cluster AChRs at the NMJ, and breeding them with transgenic mice constitutively expressing Z agrin in motor neurons rescued AChR clustering. Surprisingly, however, these rescued mice remained paralyzed, while electrophysiologic studies demonstrated that the motor axon and synapse were functional-spontaneous and evoked recordings revealed synaptic transmission and muscle contraction. These results point to a proximal defect in motor neuron firing in the absence of Nova and reveal a previously unsuspected role for RNA regulation in the physiologic activation of motor neurons. IS - 9 JF - Proceedings of the National Academy of Sciences EP - 3518 TI - Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing VL - 106 SP - 3513 KW - agrin AU - Ruggiu, Matteo AU - Herbst, Ruth AU - Kim, Natalie AU - Jevsek, Marko AU - Fak, John AU - Mann, Mary AU - Fischbach, Gerald AU - Burden, Steven AU - Darnell, Robert PY - 2009/03/03/ UR - http://dx.doi.org/10.1073/pnas.0813112106 ER -