The Enterins: A Novel Family of Neuropeptides Isolated from the Enteric Nervous System and CNS of Aplysia

Abstract

To identify neuropeptides that have a broad spectrum of actions on the feeding system of Aplysia, we searched for bioactive peptides that are present in both the gut and the CNS. We identified a family of structurally related nonapeptides and decapeptides (enterins) that are present in the gut and CNS of Aplysia, and most of which share the HSFVamide sequence at the C terminus. The structure of the enterin precursor deduced from cDNA cloning predicts 35 copies of 20 different enterins. Northern analysis, in situ hybridization, and immunocytochemistry show that the enterins are abundantly present in the CNS and the gut of Aplysia. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry we characterized the enterin-precursor processing, demonstrated that all of the precursor-predicted enterins are present, and determined post-translational modifications of various enterins. Enterin-positive neuronal somata and processes were found in the gut, and enterins inhibited contractions of the gut. In the CNS, the cerebral and buccal ganglia, which control feeding, contained the enterins. Enterin was also present in the nerve that connects these two ganglia. Enterins reduced the firing of interneurons B4/5 during feeding motor programs. Such enterin-induced reduction of firing also occurred when excitability of B4/5 was tested directly. Because reduction of B4/5 activity corresponds to a switch from egestive to ingestive behaviors, enterin may contribute to such program switching. Furthermore, because enterins are present throughout the nervous system, they may also play a regulatory role in nonfeeding behaviors of Aplysia.

Isolation and Characterization of Glutaminyl Cyclases from Drosophila: Evidence for Enzyme Forms with Different Subcellular Localization

“…In mammals, the formation of pGlu hormones and proteins is catalyzed by the enzyme glutaminyl cyclase. The presence of pyroglutamyl peptides, preferably neuropeptides, has been also described in arthropods and even in the mollusk Aplysia, strongly implying evolutionary conserved mechanisms of pGlu peptide functions and their formation (15,32,33). The isolation of glutaminyl cyclases from D. melanogaster described here strongly implies evolutionarily well-conserved mechanisms of pGlu peptide formation and, presumably, represents an effective machinery to confer hormonal activity.…”

The evolutionary origin of bilaterian smooth and striated myocytes

“…Interestingly, an enteric nervous system has been found in most bilaterians investigated, including Platynereis (this study), earthworms (Barna et al, 2001; Csoknya et al, 1991; Telkes et al, 1996), snails (Furukawa et al, 2001), insects (Copenhaver and Taghert, 1989), nematodes (Brownlee et al, 1994) and echinoderms (García-Arrarás et al, 1991, 2001). This suggests that the urbilaterian ancestor already possessed enteric neurons.…”

Localization of biogenic amines in the foregut of Aplysia californica: Catecholaminergic and serotonergic innervation

“…The digestive system of Aplysia is richly innervated by a broad spectrum of neuroregulators that participate in both motor and sensory functions (Lloyd et al, 1988; Miller et al, 1991,1992; Fujisawa et al., 1999; Furukawa et al, 2001, 2003). Our observations indicate that the biogenic amines dopamine and serotonin are preferentially associated with En 2 , the esophageal nerve branch that innervates the pharynx and most anterior esophagus.…”