Activity-dependent regulation of alternative splicing patterns in the rat brain

Alternative splicing plays an important role in the expression of genetic i nformation. Among the best understood alternative splicing factors are tran sformer and transformer-2, which regulate sexual differentiation in Drosoph ila. Like the Drosophila genes, the recently identified mammalian homologue s are subject to alternative splicing. Using an antibody directed against t he major human transformer-2 beta isoform, we show that it has a widespread expression in the rat brain. Pilocarpine-induced neuronal activity changes the alternative splicing pattern of the human transformer-2-beta gene in t he brain. After neuronal stimulation, a variant bearing high similarity to a male-specific Drosophila tra-2(179) isoform is switched off in the hippoc ampus and is detectable in the cortex. In addition, the ratio of another sh ort RNA isoform (htra2-beta2) to htra2-beta1 is changed. Htra2-beta2 is Rot translated into protein, and probably helps to regulate the relative amoun ts of htra2-beta1 to beta3. We also observe activity-dependent changes in a lternative splicing of the clathrin light chain B, c-src and NMDAR1 genes, indicating that the coordinated change of alternative splicing patterns mig ht contribute to molecular plasticity in the brain.