Nuclear Paxillin Modulates Alternative Splicing Programs in Neurons during Sensitive Periods of Brain Development

ABSTRACT: During sensitive postnatal periods, brain neural circuits undergo significant refinement coincident with widespread occurrence of neuronal alternative splicing events in which hundreds of genes alter splice site selection to generate isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent serine119 phosphorylation of paxillin (p-PaxillinS119) acts as a molecular switch in the nucleus to modulate alternative splicing during this period. We report that following NMDA receptor activation, nuclear p-PaxillinS119 is recruited to nuclear speckles, where it interacts with U2AFs and splicing factors. Neuronal paxillin expression is required for timely alternative splicing of synaptic factors, including Snap25. Consequently, young mice lacking paxillin S119 phos

SUBMITTER: Pei-Lin Cheng 

PROVIDER: S-BIAD2143 | bioimages |

REPOSITORIES: bioimages