Functional hypervariability and gene diversity of cardioactive neuropeptides

Area of Science:

• Neuroendocrinology
• Comparative Physiology
• Molecular Biology

Background:

• Crustacean cardioactive peptide (CCAP) and related peptides are vital neurohormones in invertebrates.
• CCAP typically functions as a cardio-accelerator in arthropods.

Purpose of the Study:

• To isolate and characterize CCAP-related peptides from the cone snail Conus villepinii.
• To investigate the physiological effects of these novel peptides, termed conoCAPs, on cardiac function.
• To compare the functions of molluscan conoCAPs with arthropod CCAP.

Main Methods:

• Isolation of conoCAP-a from Conus villepinii venom.
• Cloning of the precursor cDNA for conoCAP-a, revealing conoCAP-b and conoCAP-c.
• In vivo studies on Drosophila larvae and rats to assess cardiac effects.
• In vitro studies on rat ventricular cardiac myocytes to investigate cellular mechanisms.

Main Results:

• The conoCAP precursor encodes three distinct CCAP-like peptides.
• ConoCAP-a exhibited cardio-inhibitory effects in Drosophila larvae and rats, decreasing heart rate and blood pressure.
• ConoCAP-a reduced systolic calcium in rat cardiac myocytes, suggesting impaired intracellular calcium handling.
• Arthropod CCAP showed no cardiac effects in rats, highlighting functional divergence.

Conclusions:

• Molluscan CCAP-like peptides (conoCAPs) possess distinct physiological functions compared to arthropod CCAP.
• The multi-peptide precursor organization allows for biological diversification without gene duplication.
• Sequence variability in molluscan CCAP-like peptides contributes to functional hypervariability and adaptive evolution.