Alternative Splicing of Neurofibromatosis Type 1 Exon 23a Modulates Ras/ERK Signaling and Learning Behaviors in Mice

Neurofibromin is one of the few Ras-GTP activating proteins (Ras-GAPs) expressed in the brain. Disruption of its expression leads to the detrimental disease neurofibromatosis type 1 (NF1). Many studies have revealed the crucial role of NF1 in developing and adult tissues. However, these studies have focused on the expression of the entire NF1 gene and largely ignored the role of an alternative splicing event that controls the Ras-GAP function of neurofibromin. The focus of this chapter is NF1 exon 23a. This exon is located in the GAP-related domain (GRD) of neurofibromin. Its expression level, indicated by the percentage of its inclusion in the NF1 mRNA transcripts, has a profound effect on the Ras-GAP function of neurofibromin. In this chapter, we review the expression pattern of exon 23a and the molecular mechanisms that regulate its expression. We then discuss the role of its expression in Ras/ERK signaling and learning behaviors in mice. Lastly, we propose a few directions for future studies.