Neurohormones and Neurohormone Receptors in Invertebrates

Abstract

Neuropeptides and their receptors play an extremely important role in invertebrates. From the lowest invertebrate group having a nervous system, the cnidarians, we isolated about 30 different neuropeptides, and this can be regarded as being the tip of an iceberg. The cnidarian neuropeptides are located in densecored neurosecretory vesicles and are biologically active as neurotransmitters or neurohormones. We have also cloned the preprohormones of the cnidarian neuropeptides. These preprohormones have a very high copy number (up to 36) of the immature neuropeptide sequence. In addition to well-known “classical” processing enzymes, novel processing enzymes must be present in cnidarian neurones, making neuropeptide biosynthesis in cnidarians more complex than in higher organisms. In 1993, in an attempt to clone the receptors for the cnidarian neurohormones, we found that sea anemones produce a receptor that shows a striking structural homology with members of the mammalian glycoprotein hormone (TSH, FSH, LH/CG) receptor family. This was an exciting finding, since glycoprotein hormone receptors had, at that time, only been cloned from mammals. Our results suggested that glycoprotein hormones and possibly all the processes that are mediated by these types of receptors are conserved throughout the animal kingdom, from cnidarians to mammals. We then focused on insects and cloned a Drosophila receptor that, again, showed a strong homology, both at the protein and gene levels, with the mammalian glycoprotein hormone receptors. The Drosophila receptor gene is strongly expressed starting 8–16 h after oviposition and the expression stays high until after pupation. This suggests that the receptor is involved in insect development. From these examples in cnidarians and insects, it is clear that several hormonal systems, such as the neuropeptide/receptor and glycoprotein hormone/receptor couples have a long evolutionary history.