Abstract
Orexins are excitatory neuropeptides, which are predominantly associated with feeding behavior, sleep-wake cycle and energy homeostasis. The orexinergic system comprises of HCRTR1 and HCRTR2, G-protein-coupled receptors of rhodopsin family and the endogenous ligands processed from HCRT pro-hormone, Orexin A and Orexin B. These neuropeptides are biosynthesized by the orexin neurons present in the lateral hypothalamus area, with dense projections to other brain regions. The orexin-receptor signaling is implicated in various metabolic as well as neurological disorders, making it a promising target for pharmacological interventions. However, there is limited information available on the collective representation of the signal transduction pathways pertaining to the orexin-orexin receptor signaling system. Here, we depict a compendium of the Orexin A/B stimulated reactions in the form of a basic signaling pathway map. This map catalogs the reactions into five categories: molecular association, activation/inhibition, catalysis, transport, and gene regulation. A total of 318 downstream molecules were annotated adhering to the guidelines of NetPath curation. This pathway map can be utilized for further assessment of signaling events associated with orexin-mediated physiological functions and is freely available on WikiPathways, an open-source pathway database (https://www.wikipathways.org/index.php/Pathway:WP5094).
Graphical abstract
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Abbreviations
- CNS:
-
Central Nervous System
- HCRT:
-
Hypocretin
- GPCR:
-
G protein-coupled receptor
- HCRTR1:
-
Hypocretin receptor 1
- HCRTR2:
-
Hypocretin receptor 2
- OX1R:
-
Orexin receptor 1
- OX2R:
-
Orexin receptor 2
- Ox-A:
-
Orexin A
- Ox-B:
-
Orexin B
- OXR:
-
Orexin receptors
- PPIs:
-
Protein-protein interactions
- BioPAX:
-
Biological Pathway Exchange
- SBML:
-
Systems Biology Markup Language
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- PLC:
-
Phospholipase C
- PLD:
-
Phospholipase D
- IP3 :
-
Inositol-3-phosphate
- MAPK:
-
Mitogen activated protein kinases
- GRK:
-
G Protein-Coupled Receptor Kinase
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Acknowledgements
We thank Karnataka Biotechnology and Information Technology Services (KBITS), Government of Karnataka for the support to the Center for Systems Biology and Molecular Medicine at Yenepoya (Deemed to be University) under the Biotechnology Skill Enhancement Programme in Multiomics Technology (BiSEP GO ITD 02 MDA 2017). We thank the Department of Biotechnology, Government of India for research support to the Institute of Bioinformatics (IOB), Bangalore. Oishi Chatterjee and Lathika Gopalakrishnan are recipients of the DST-INSPIRE Fellowship (SRF) from the Department of Science and Technology (DST), Government of India. Rajesh Raju is a recipient of the Young Scientist Award (YSS/2014/000607) from the Science and Engineering Research Board, Department of Science and Technology (DST), Government of India.
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Chatterjee, O., Gopalakrishnan, L., Pullimamidi, D. et al. A molecular network map of orexin-orexin receptor signaling system. J. Cell Commun. Signal. 17, 217–227 (2023). https://doi.org/10.1007/s12079-022-00700-3
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DOI: https://doi.org/10.1007/s12079-022-00700-3