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Abstract Neuropeptide Y (NPY) is an evolutionarily conserved neurosecretory molecule implicated in a diverse complement of functions across taxa and in regulating feeding behavior and reproductive maturation inOctopus. However, little is known about the precise molecular circuitry of NPY‐mediated behaviors and physiological processes, which likely involve a complex interaction of multiple signal molecules in specific brain regions. Here, we examined the expression of NPY throughout theOctopuscentral nervous system. The sequence analysis ofOctopusNPY precursor confirmed the presence of both, signal peptide and putative active peptides, which are highly conserved across bilaterians.In situhybridization revealed distinct expression of NPY in specialized compartments, including potential “integration centers,” where visual, tactile, and other behavioral circuitries converge. These centers integrating separate circuits may maintain and modulate learning and memory or other behaviors not yet attributed to NPY‐dependent modulation inOctopus. Extrasomatic localization of NPY mRNA in the neurites of specific neuron populations in the brain suggests a potential demand for immediate translation at synapses and a crucial temporal role for NPY in these cell populations. We also documented the presence of NPY mRNA in a small cell population in the olfactory lobe, which is a component of theOctopusfeeding and reproductive control centers. However, the molecular mapping of NPY expression only partially overlapped with that produced by immunohistochemistry in previous studies. Our study provides a precise molecular map of NPY mRNA expression that can be used to design and test future hypotheses about molecular signaling in variousOctopusbehaviors.
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Structural basis of neuropeptide Y signaling through Y1 receptor
Abstract Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (Y1R) in complex with Gi1protein. The NPY C-terminal segment forming the extended conformation binds deep into the Y1R transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with Y1R extracellular loops, contributing to the high affinity of NPY for Y1R. The structural analysis of NPY-bound Y1R and mutagenesis studies provide molecular insights into the activation mechanism of Y1R upon NPY binding.
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- Award ID(s):
- 2111728
- PAR ID:
- 10363228
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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