Related Experiment Video
Updated: Dec 21, 2025
Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
G-Protein-Coupled Receptor SRBC-48 Protects against Dendrite Degeneration and Reduced Longevity Due to Infection
Supender Kaur1, Alejandro Aballay1
1Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
Abstract:
Increasing evidence suggests that deficient immune modulation and microbial infections underline neurodegeneration, but the mechanisms remain obscure. Here, we show that the G-protein-coupled receptor (GPCR) SRBC-48, which belongs to the class BC serpentine receptors, has a protective role in Caenorhabditis elegans dendrite degeneration caused by Pseudomonas aeruginosa infection. Our results indicate that SRBC-48 functions in a cell-autonomous manner in AWC neurons to protect against infection-associated dendrite degeneration. The absence of SRBC-48 results in a reduced lifespan caused by a pathogen infection early in life that induces dendrite degeneration. The decreased longevity in animals deficient in SRBC-48 is due to uncontrolled activation of immune genes, particularly those regulated by the FOXO family transcription factor DAF-16 that is part of the insulin/insulin-like growth factor (IGF)-1 receptor homolog DAF-2. These results reveal how an infection early in life can not only induce dendrite degeneration but also reduce lifespan.
Insights
The G-protein-coupled receptor SRBC-48 protects against neurodegeneration from Pseudomonas aeruginosa infection in C. elegans. Its absence shortens lifespan due to uncontrolled immune gene activation.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Neurodegenerative diseases are increasingly linked to immune dysfunction and microbial infections.
- The precise molecular mechanisms underlying these connections remain largely unknown.
Purpose of the Study:
- To investigate the role of the G-protein-coupled receptor (GPCR) SRBC-48 in protecting against neurodegeneration caused by Pseudomonas aeruginosa infection.
- To elucidate the cellular and molecular pathways involved in infection-induced dendrite degeneration and lifespan reduction.
Main Methods:
- Utilized Caenorhabditis elegans as a model organism.
- Investigated the function of SRBC-48 in AWC neurons.
- Analyzed the impact of SRBC-48 deficiency on dendrite degeneration, lifespan, and immune gene expression, focusing on the DAF-16/DAF-2 pathway.
Main Results:
- SRBC-48 exhibits a protective function against Pseudomonas aeruginosa-induced dendrite degeneration in C. elegans.
- SRBC-48 acts in a cell-autonomous manner within AWC neurons.
- Absence of SRBC-48 leads to reduced lifespan following early-life infection, characterized by dendrite degeneration.
- Deficiency in SRBC-48 results in uncontrolled immune gene activation, particularly those regulated by DAF-16.
Conclusions:
- SRBC-48 plays a crucial role in mitigating neurodegeneration and lifespan reduction associated with microbial infections.
- The findings highlight the intricate link between early-life infections, immune responses, and long-term health outcomes, including neurodegeneration and longevity.
- Uncontrolled immune activation, mediated by the DAF-16 pathway, contributes to decreased lifespan in the absence of SRBC-48.
Related Concept Videos
01:12GPCR Desensitization
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...