The β integrin modulates serotonin sensitivity via NPxY motifs to regulate egg laying and mechanosensation behaviors in Caenorhabditis elegans
Year: 2025
Type: article
Abstract: BACKGROUND: Integrin is an αβ heterodimeric receptor to the extracellular matrix; its binding to the matrix recruits focal adhesions to two NPxY motifs, the tyrosine phosphorylation sites in the cytoplasmic domain. Studies found that replacing tyrosines (Y) with phenylalanines (F) in the motif of β1 integrin displayed little developmental or behavioral defects. However, the tyrosine-to-alanine (A) caused embryonic lethality. RESULTS: . The double non-phosphorylatable pat-3(YYFF) mutant exhibited serotonin hypersensitivity and defective egg retention. The phosphomimetic NPxY, pat-3(Y804E), mutant displayed reduced egg laying in response to serotonin and fluoxetine, suggesting that the NPxY phosphorylation is associated with vulval contraction and serotonin sensitivity. Additionally, pat-3(Y792A), pat-3(Y792F), pat-3(Y804E), and pat-3(YYFF) mutants exhibited mechanosensation defects, demonstrating that NPxY phosphorylation regulates sensory neuron activity. Further analysis revealed that exogenous serotonin reduced mechanosensation, while blocking serotonin secretion rescued the mechanosensation of pat-3 NPxY mutants, suggesting that integrin NPxY modulates serotonin levels in C. elegans. CONCLUSION: Our results underscore the functional importance of pat-3 NPxY motifs in muscle and neurons, potentially linking integrin NPxY motifs to neurotransmitter response and mechanosensory functions.
Source: Developmental Dynamics
DOI: 10.1002/dvdy.70090
Authors: Josh Haram Bumm, Daniel Dogeon Lee, Zhongqiang Qiu, Angela Haeun Choi, Meghana Kolluri, Michael J. Olsen, Lianzijun Wang, Myeongwoo Lee
Institution: Baylor University
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,430
OpenAlex ID: W4415396594