Stimulus‐dependent regulation and cellular expression of genes encoding neuropeptides, prohormone convertases, α‐amidating enzyme and 7B2 in identified Lymnaea neurons

Abstract

Synthesis of bioactive peptides is regulated by several posttranslational processing events, including cleavage of peptides from a prohormone, and chemical modifications. Using quantitative in situ hybridization and neuron-specific macroarrays, we first demonstrated cell-type specific expression levels of transcripts encoding prohormone convertases, peptide a-amidating enzyme as well as the chaperone 7B2 in Lymnaea neurons. Second, we demonstrated a strict correlation between a-amidating enzyme and its neuropeptide substrates. However, this strict relationship of gene expression of the three prohormone convertases and types of cleavage site used is not present. Third, we showed by a physiological stimulus, i.e. clean water, which leads to a stereotyped egg-laying behaviour resulting in successful eggmass deposition, the co-regulated induction of transcript levels of processing enzymes, 7B2, and egg-laying hormone. These data indicate that (i) these enzymes (and chaperone) are involved in egg-laying hormone neuropeptide biosynthesis, and (ii) neuropeptide release and transcript levels of both prohormones and processing enzymes are regulated in accordance with physiological demands.

Reduced expression of neuropeptide genes in a genome‐wide screen of a secretion‐deficient mouse

“…Because genes encoding other released substances, such as BDNF, fibroblast growth factor 1 and reelin, were also differentially expressed, a general feedback mechanism may exist, adjusting gene expression to the ‘consumption’ of its product. Such a feedback mechanism is in line with several studies in which physiological stimulation was found to induce the expression of secreted products (see, for instance, Spijker et al . 2004b).…”