The evolution and functional significance of neuropeptide cocktails: insights from SALMFamides in asteroid echinoderms.
SALMFamide neuropeptides in starfish are giving researchers a closer look at how peptide “cocktails” evolve and function. The latest work from Queen Mary University of London dives into these neuropeptide clusters, revealing how multiple, structurally similar peptides are packed into single precursors—and what that actually means for receptor activity.
Open Biol
by Escudero Castelán N, Elphick MR
“The evolution and functional significance of neuropeptide cocktails: insights from SALMFamides in asteroid echinoderms. Escudero Castelán N(1), Elphick MR(1). Author information: (1)School of Biological & Behavioural Sciences, Queen Mary University of London , London, UK. Neuropeptides derived from larger precursor proteins are neuronal signalling molecules that regulate physiological processes and behaviour. Some precursors, particularly in invertebrates, give rise to 'cocktails' of structurally related neuropeptides, but the functional significance of this phenomenon is poorly understood. Here, we investigate this by analysing the evolution and receptor pharmacology of SALMFamide-type neuropeptides in starfish (class Asteroidea, phylum Echinodermata). Two types of SALMFamide precursors occur in echinoderms: L-type and F-type, which contain neuropeptides that typically have C-terminal LxF-NH2 and FxF-NH2 motifs (x is variable), respectively. In starfish, L-type and F-type precursors typically contain seven and nine neuropeptides, respectively, but taxon-specific loss/gain of neuropeptides has occurred. Experimental tests revealed that most neuropeptides derived from L-type and F-type precursors in the starfish Asterias rubens exhibit similar potency/efficacy as ligands for their kisspeptin-type receptors, ArKPR7 and ArKPR6, respectively. However, the N-terminally positioned neuropeptide in each precursor has lower potency/efficacy. Furthermore, one neuropeptide derived from the F-type precursor exhibits convergent similarity with L-type precursor-derived neuropeptides, but it has low potency as a ligand for ArKPR7. Our findings indicate that structurally related neuropeptides derived from the same precursor are functionally redundant as receptor ligands; therefore, loss of neuropeptides and/or neuropeptide bioactivity can occur. © 2026 The Authors.”
Here’s the gist. In starfish (Asteroidea), there are two main SALMFamide precursors: L-type and F-type. Each precursor churns out a set of neuropeptides—seven for L-type, nine for F-type—distinguished by their signature C-terminal motifs. But the number and type can shift with evolutionary tweaks, leading to species-specific gains or losses.
The team tested how these peptides interact with starfish kisspeptin-type receptors, ArKPR7 and ArKPR6. Most of the peptides acted similarly as ligands—same potency, same efficacy. The outlier was the first (N-terminal) peptide in each precursor, which showed weaker action. There’s also a case of convergent evolution: an F-type peptide mimics the structure of L-type peptides but still doesn’t hit the mark as a strong ligand.
Key takeaway: Most SALMFamide neuropeptides from the same precursor are functionally redundant at the receptor level. That redundancy means the loss or modification of some peptides during evolution isn’t a big deal for basic signaling.
Why should researchers care?
Peptide cocktails aren’t just biochemical noise. They reveal how redundancy and diversity shape signaling systems.
The kisspeptin receptor findings open up new questions about how neuropeptidergic systems adapt and specialize.
For anyone working with kisspeptin or interested in sourcing peptide precursors, understanding peptide redundancy is key. Check the vendor directory for the latest suppliers and options.
Bottom line: Neuropeptide cocktails aren’t just evolutionary leftovers—they’re a toolkit for signaling flexibility.
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