Abstract
BackgroundNicotinic and muscarinic acetylcholine receptors likely evolved in the cnidarian–bilaterian common ancestor. Both receptor families are best known for their role at chemical synapses in bilaterian animals, but they also have described roles as non-neuronal signaling receptors within the bilaterians. It is not clear when either of the functions for nicotinic or muscarinic receptors evolved. Previous studies in cnidarians suggest that acetylcholine’s neuronal role existed prior to the cnidarian–bilaterian divergence, but did not address potential non-neuronal functions. To determine the origins of neuronal and non-neuronal functions of nicotinic acetylcholine receptors, we investigated the phylogenetic position of cnidarian acetylcholine receptors, characterized the spatiotemporal expression patterns of nicotinic receptors in N. vectensis, and compared pharmacological studies in N. vectensis to the previous work in other cnidarians.ResultsConsistent with described activity in other cnidarians, treatment with acetylcholine-induced tentacular contractions in the cnidarian sea anemone N. vectensis. Phylogenetic analysis suggests that the N. vectensis genome encodes 26 nicotinic (nAChRs) and no muscarinic (mAChRs) acetylcholine receptors and that nAChRs independently radiated in cnidarian and bilaterian linages. The namesake nAChR agonist, nicotine, induced tentacular contractions similar to those observed with acetylcholine, and the nAChR antagonist mecamylamine suppressed tentacular contractions induced by both acetylcholine and nicotine. This indicated that tentacle contractions are in fact mediated by nAChRs. Nicotine also induced the contraction of radial muscles, which contract as part of the peristaltic waves that propagate along the oral–aboral axis of the trunk. Radial contractions and peristaltic waves were suppressed by mecamylamine. The ability of nicotine to mimic acetylcholine responses, and of mecamylamine to suppress acetylcholine and nicotine-induced contractions, supports a neuronal function for acetylcholine in cnidarians. Examination of the spatiotemporal expression of N. vectensis nAChRs (NvnAChRs) during development and in juvenile polyps identified that NvnAChRs are expressed in neurons, muscles, gonads, and large domains known to be consistent with a role in developmental patterning. These patterns are consistent with nAChRs functioning in both a neuronal and non-neuronal capacity in N. vectensis.ConclusionOur data suggest that nAChR receptors functioned at chemical synapses in N. vectensis to regulate tentacle contraction. Similar responses to acetylcholine are well documented in cnidarians, suggesting that the neuronal function represents an ancestral role for nAChRs. Expression patterns of nAChRs are consistent with both neuronal and non-neuronal roles for acetylcholine in cnidarians. Together, these observations suggest that both neuronal and non-neuronal functions for the ancestral nAChRs were present in the cnidarian–bilaterian common ancestor. Thus, both roles described in bilaterian species likely arose at or near the base of nAChR evolution.
Highlights
Nicotinic and muscarinic acetylcholine receptors likely evolved in the cnidarian–bilaterian common ancestor
Acetylcholine treatment induces tentacle contractions in N. vectensis We first set out to determine if N. vectensis would have responses to acetylcholine similar to those observed in other cnidarians [21,22,23, 46]. 15% of control animals treated with Nematostella growth medium contract their tentacles (Figs. 1A–D, 3H, 4A–C, P; Additional file 5: Video S1)
We tested a dose response of acetylcholine using 1 μM to 25 mM, because this range of concentrations was shown to be effective in other cnidarians [22,23,24]
Summary
Nicotinic and muscarinic acetylcholine receptors likely evolved in the cnidarian–bilaterian common ancestor Both receptor families are best known for their role at chemical synapses in bilaterian animals, but they have described roles as non-neuronal signaling receptors within the bilaterians. It is not clear when either of the func‐ tions for nicotinic or muscarinic receptors evolved. The nAChRs and mAChRs have been well characterized in bilaterian species (insects, vertebrates, annelids, echinoderms, hemichordates, mollusks, nematodes, etc.) They are expressed in a wide range of tissues, and are known to function as receptors for cell signaling regulating cellto-cell contact, proliferation, differentiation, migration, gene expression, and apoptosis in responding cells [2,3,4]. NAChRs and mAChRs are most well known for their role in chemical synapses, where they regulate the excitability of neurons and muscles [2, 5]
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