The infective juveniles (IJs) of entomopathogenic nematode (EPN) find and infect their host insects in heterogeneous soil ecosystems by sensing a universal host cue (CO) or insect/plant-derived odorants, which bind to various sensory receptors, including G protein-coupled receptors (GPCRs). Nematode chemosensory GPCRs (NemChRs) bind to a diverse set of ligands, including odor molecules. However, there is a lack of information on the NemChRs in EPNs. Here we identified 21 GPCRs in the genome sequence in a triphasic manner, combining various transmembrane detectors and GPCR predictors based on different algorithms, and considering inherent properties of GPCRs. The pipeline was validated by reciprocal BLAST, InterProscan, GPCR-CA, and NCBI CDD search. Functional classification of predicted GPCRs using Pfam revealed the presence of four NemChRs. Additionally, GPCRs were classified into various families based on the reciprocal BLAST approach into a frizzled type, a secretin type, and 19 rhodopsin types of GPCRs. Gi/o is the most abundant kind of G-protein, having a coupling specificity to all the fetched GPCRs. As the 21 GPCRs identified are expected to play a crucial role in the host-seeking behavior, these might be targeted to develop novel insect-pest management strategies by tweaking EPN IJ behavior, or to design novel anthelminthic drugs. Our new and stringent GPCR detection pipeline may also be used to identify GPCRs from the genome sequence of other organisms.
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http://dx.doi.org/10.2478/jofnem-2023-0038 | DOI Listing |
Andrology
January 2025
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
The neuroendocrine system that comprises the glycoprotein hormones (GpHs) and their receptors is essential for reproduction and metabolism. Each GpH hormone is an αβ heterodimer of cystine-knot proteins and its cognate receptor is a G-protein coupled receptor (GPCR) distinguished by a large leucine-rich-repeat (LRR) extracellular domain that binds the hormone and a class A GPCR transmembrane domain that signals through an associating heterotrimeric G protein. Hence, the receptors are called LRR-containing GPCRs-LGRs.
View Article and Find Full Text PDFNature
January 2025
Department of Genetics, Stanford University, Stanford, CA, USA.
Biochim Biophys Acta Rev Cancer
January 2025
National Clinical Research Center for Child Health of the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China. Electronic address:
G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that play a crucial role in signal transduction and cellular communication. GPCR proteins are involved in a wide range of physiological processes, including cell growth, migration, and survival. Dysregulation of GPCR protein expression has been implicated in the pathogenesis of various diseases, including cancer, and GPCR proteins have been shown to modulate these processes in various types of cancer, highlighting their importance as potential therapeutic targets.
View Article and Find Full Text PDFPharmacol Ther
January 2025
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.
G protein-coupled receptors (GPCRs) can transmit signals via G protein-dependent or independent pathways due to the conformational changes of receptors and ligands, which is called biased signaling. This concept posits that ligands can selectively activate a specific signaling pathway after receptor activation, facilitating downstream signaling along a preferred pathway. Biased agonism enables the development of ligands that prioritize therapeutic signaling pathways while mitigating on-target undesired effects.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Microbiology and Immunology, Graduate School of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
G protein-coupled receptors (GPCRs), critical for cellular communication and signaling, represent the largest cell surface protein family and play important roles in numerous pathophysiological processes. Consequently, GPCRs have become a primary focus in drug discovery efforts. Beyond their traditional G protein-dependent signaling pathways, GPCRs are also capable of activating alternative signaling mechanisms, including G protein-independent signaling, biased signaling, and signaling crosstalk.
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