depolarization and cam kinase iv modulate nmda receptor splicing through two essential rna elements去极化和凸轮第四激酶调节门冬氨酸受体通过两个重要rna拼接元素.pdfVIP

PLoS BIOLOGY Depolarization and CaM Kinase IV Modulate NMDA Receptor Splicing through Two Essential RNA Elements 1 2,3¤ 1 4 2,3 1,5* Ji-Ann Lee , Yi Xing , David Nguyen , Jiuyong Xie , Christopher J. Lee , Douglas L. Black 1 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America, 2 Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, United States of America, 3 Molecular Biology Institute, Center for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, California, United States of America, 4 Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada, 5 Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, California, United States of America Alternative splicing controls the activity of many proteins important for neuronal excitation, but the signal- transduction pathways that affect spliced isoform expression are not well understood. One particularly interesting system of alternative splicing is exon 21 (E21) of the NMDA receptor 1 (NMDAR1 E21), which controls the trafficking of þþ NMDA receptors to the plasma membrane and is repressed by Ca /calmodulin-dependent protein kinase (CaMK) IV signaling. Here, we characterize the splicing of NMDAR1 E21. We find that E21 splicing is reversibly repressed by neuronal depolarization, and we identify two RNA elements within the