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The Nociceptive Activity of Peripheral Sensory Neurons is Modulated by the Neuronal Membrane Proteasome

GSE261727 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2024/04/12 Platform GPL24247
Summary
Proteasomes are critical for peripheral nervous system (PNS) function. Here, we investigate mammalian PNS proteasomes and reveal the presence of the neuronal membrane proteasome (NMP). We show that specific inhibition of the NMP on distal nerve fibers innervating the mouse hind paw leads to reduction in mechanical and pain sensitivity. Investigating PNS NMPs we demonstrate their presence on the somata, proximal, and distal axons of a subset of dorsal root ganglion (DRG) neurons. Single-cell RNA sequencing experiments reveal that the NMP expressing DRGs are primarily MrgprA3+ and Cysltr2+. NMP inhibition in DRG cultures leads to cell autonomous and non-cell autonomous changes in Ca2+ signaling induced by KCl depolarization, ab-meATP, or the pruritogen histamine. Taken together, these data support a model whereby NMPs are expressed on a subset of somatosensory DRGs to modulate signaling between neurons of distinct sensory modalities and indicate the NMP as a potential target for controlling pain
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Also filed as BioProject PRJNA1088500 and SRA study SRP495503. Searching any of these in the dataset finder brings you back here.

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