Abstract
Post-translational modifications (PTMs) diversify peptide structure and allow for greater flexibility within signaling networks. The cardiac neuromuscular system of the American lobster, Homarus americanus, is made up of a central pattern generator, the cardiac ganglion (CG), and peripheral cardiac muscle. Together, these components produce flexible output in response to peptidergic modulation. Here, we examined the role of PTMs in determining the effects of a cardioactive neuropeptide, myosuppressin (pQDLDHVFLRFamide), on the whole heart, the neuromuscular junction/muscle, the isolated CG, and the neurons of the CG. Mature myosuppressin and noncyclized myosuppressin (QDLDHVFLRFamide) elicited similar and significant changes in whole heart contraction amplitude and frequency, stimulated muscle contraction amplitude and the bursting pattern of the intact and ligatured neurons of the ganglion. In the whole heart, nonamidated myosuppressin (pQDLDHVFLRFG) elicited only a small decrease in frequency and amplitude. In the absence of motor neuron input, nonamidated myosuppressin did not cause any significant changes in the amplitude of stimulated contractions. In the intact CG, nonamidated myosuppressin elicited a small but significant decrease in burst duration. Further analysis revealed a correlation between the extent of modulation elicited by nonamidated myosuppressin in the whole heart and the isolated, intact CG. When the neurons of the CG were physically decoupled, nonamidated myosuppressin elicited highly variable responses. Taken together, these data suggest that amidation, but not cyclization, is critical in enabling this peptide to exert its effects on the cardiac neuromuscular system.NEW & NOTEWORTHY Myosuppressin (pQDLDHVFLRFamide), a well-characterized crustacean neuropeptide, and its noncyclized (QDLDHVFLRFamide) and nonamidated (pQDLDHVFLRFG) isoforms alter the output of the cardiac neuromuscular system of the American lobster, Homarus americanus. Mature myosuppressin and noncyclized myosuppressin elicited similar and significant changes across all levels of the isolated system, whereas responses to nonamidated myosuppressin were significantly different from other isoforms and were highly variable. These data support the diversity of peptide action as a function of peptide structure.
Highlights
Central pattern generators (CPGs) are neural networks that produce rhythmic electrical outputs in the absence of sensory or central input
Following enzymatic cleavage within the neurosecretory pathway, peptides undergo a variety of post-translational modifications (PTMs), including carboxy (C)terminal amidation, cyclization of N-terminal glutamine/ glutamic acid (Q/E) residues, disulfide bridging between cysteines, and sulfation of tyrosines [5]
Because fully modified myosuppressin (“mature myosuppressin”) includes two PTMs, an N-terminal cyclization of the pyroglutamate residue and a C-terminal amidation, and recent work has demonstrated that the presence of a myosuppressin isoform lacking at least one of these PTMs in Homarus neural tissues [19], we asked what role these PTMs played in determining the effect of myosuppressin on the cardiac neuromuscular system
Summary
Central pattern generators (CPGs) are neural networks that produce rhythmic electrical outputs in the absence of sensory or central input. Circulating and locally released neuromodulators allow for flexibility in the neuronal output that underlies a variety of patterned movements such as chewing and walking [1, 2]. Various chemical molecules can serve as neuromodulators, peptides are the most expansive and diverse group [3,4,5]. PTMs are important mechanisms that diversify peptide function and increase the functional flexibility of complex networks [6]. These structural alterations regulate the interactions of molecules, maintain the stability of peptides, and play
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