Localization and functional roles of corticotropin-releasing factor receptor type 2 in the cerebellum

The corticotropin-releasing factor (CRF) type 2 receptor has three splice variants alpha, beta, and gamma. In the rodent brain only CRF-R2 alpha is present. In the cerebellum, CRF-R2 alpha has two different isoforms: a full-length form (fl) and truncated (tr). Both forms CRF-R2 have a unique cellular distribution. During postnatal cerebellar development, the expression patterns of tr and fl isoforms are changing. This suggests that, CRF and the related peptide urocortin (UCN) could play distinct roles in the immature and adult cerebellum, acting via different receptors subtypes. This review focuses on differences in the distribution of each isoform of CRF-R2 in view of their relationship to CRF and UCN release sites and their possible functional implications. Moreover, it includes novel findings of molecular pathways activating CRF-R2 isoforms through which CRF and UCN excert their specific actions.