Figure 6

Figure 6

A model illustrating the role of alternative splicing of PAC1 hop cassette that serves as an ON/OFF stress switch. In response to various stressors, the so called PAC1-null splice variant (i.e., no deletion in the N-terminal domain and no addition to the intracellular loops) modulate transcriptional activation of CRH and stress behaviors to adapt to the changes in homeostasis. Termination of CRH-mediated stress response is mediated by means of regulation of PAC1 gene splicing and inclusion of an altered exon (hop1) encoding to 28 amino acids of the third intracellular loop leading to the formation of the PAC1-hop1 splice variant. Generation of the PAC1-hop isoform terminates stress response by means yet to be uncovered (see text and Amir-Zilberstein et al., 2012).