Transcriptional and Post-Transcriptional Regulation of Oxytocin and Vasopressin Gene Expression by CREB3L1 and CAPRIN2

INTRODUCTION: Water homeostasis is achieved by secretion of peptide hormones arginine vasopressin (AVP) and oxytocin (OXT) that are synthesised by separate populations of magnocellular neurones (MCNs) in the hypothalamus. To further understand the molecular mechanisms that facilitate biosynthesis of AVP and OXT by MCNs, we have explored the spatiotemporal dynamic, of two genes identified by our group as being important components of the osmotic defence response: Caprin2 and Creb3l1.

METHODS: By RNA in situ hybridization and immunohistochemistry, we have characterised the expression of Caprin2 and Creb3l1 in MCNs in the basal state, in response to dehydration, and during rehydration in the rat.

RESULTS: We found that Caprin2 and Creb3l1 are expressed in AVP and OXT MCNs and in response to dehydration expression increases in both MCN populations. Protein levels mirror the increase in transcript levels for both CREB3L1 and CAPRIN2. In view of increased CREB3L1 and CAPRIN2 expression in OXT neurones by dehydration, we explored OXT specific functions for these genes. By luciferase assays, we demonstrate that CREB3L1 may be a transcription factor regulating Oxt gene expression. By RNA immunoprecipitation assays and northern blot analysis of Oxt mRNA poly(A) tails, we have found that CAPRIN2 binds Oxt mRNA and regulates its poly(A) tail length. Moreover, in response to dehydration, Caprin2 mRNA is subjected to nuclear retention, possibly to regulate Caprin2 availability to the cytoplasm.

CONCLUSION: The exploration of the spatiotemporal dynamics of Creb3l1 and Caprin2 encoded mRNAs and proteins has provided novel insights beyond the AVP-ergic system revealing novel OXT-ergic system roles of these genes in the osmotic defence response.