Apoptotic cells as a physiological source of β-alanine to modulate MrgprD-expressing sensory neurons
Abstract
Cutaneous injury triggers sensory neurons that elicit pain or itch and modulate tissue repair. A subset of these neurons expresses the Mas-related G protein-coupled receptor MrgprD, which is selectively activated by β alanine. However, the physiological source of this endogenous metabolite has remained elusive for two decades. Here, we unexpectedly identify apoptotic cells as a physiologically relevant endogenous source of β alanine. Through an unbiased screen of G protein-coupled receptors (GPCRs) activated by metabolites released from dying cells, we detected robust activation of MrgprD. Mass spectrometry and functional assays confirmed that early-stage apoptotic cells release β alanine via the caspase-mediated opening of Pannexin 1 channels. Because MrgprD-expressing neurons innervate the epidermis, we investigated the skin and identified apoptotic keratinocytes as a potential local source of β alanine. Using three distinct models of skin perturbation, we demonstrate that MrgprD signaling directly modulates cutaneous responses. Collectively, these findings uncover a previously unrecognized signaling axis linking apoptotic metabolites to sensory neuron activation, local tissue injury responses, and the regulation of inflammation.
Committee Chair
Kodi Ravichandran
Committee Members
Claudia Han; Kendall Blumer; Marco Colona; Steven VanDyken; Xiaoxiao Wan
Degree
Doctor of Philosophy (PhD)
Author's Department
Biology & Biomedical Sciences (Molecular Cell Biology)
Document Type
Dissertation
Date of Award
8-13-2026
Language
English (en)
DOI
https://doi.org/10.7936/bapw-7j81
Recommended Citation
Gasperino, Sofia L., "Apoptotic cells as a physiological source of β-alanine to modulate MrgprD-expressing sensory neurons" (2026). Arts & Sciences Graduate Student Theses and Dissertations. 3836.
The definitive version is available at https://doi.org/10.7936/bapw-7j81