Palayyan, S. R. | bioRxiv Science

bioRxiv2026

Expression of Calca gene-derived peptides in the murine taste system

Taste cell regeneration and taste signaling are regulated by myriad growth factors and signaling molecules secreted by neurons and taste papillae - resident cells. The Calcitonin Related Polypeptide Alpha (Calca) gene is a source of four biologically active peptides with varied physiological roles. Alternative splicing of the Calca messenger RNA generates either prepro calcitonin gene related peptide (CGRP) or preprocalcitonin encoding transcripts. Proteolytic processing of preprocalcitonin generates procalcitonin, calcitonin and katacalcin. Calcitonin is a ligand for the G-protein coupled receptor calcitonin receptor (CALCR) while CGRP is a ligand for the CGRP receptor (CGRP1R) formed by the calcitonin receptor like receptor (CALCRL)-receptor activity modifying protein 1 (RAMP1) complex. Interestingly, procalcitonin too, is a ligand for the CGRP1R where it can antagonize CGRP. CGRP expression in taste and trigeminal neurons has been documented and is posited to regulate taste signaling. Single cell and bulk RNASeq of taste papillae revealed that the preprocalcitonin but not the Cgrp transcript is expressed in Tas1r3-expressing type II taste cells, while CGRP1R subunits are expressed in taste stem/progenitor cells and by subsets of fibroblasts and immune cells in the lingual mesenchyme. We confirmed this expression pattern using quantitative polymerase chain reaction (qPCR) and histological techniques. qPCR of geniculate and nodose-petrosal ganglia revealed that both express Cgrp and CGRP1R subunit mRNAs, but not preprocalcitonin and Calcr. This interesting expression patterns suggests that procalcitonin and CGRP might reciprocally regulate the CGRP1R in the taste papillae and potentially influence taste signaling, taste cell regeneration and the taste microbiome.

neuroscience↗

bioRxiv2026

Taste Papillae-associated Salivary Gland Ducts Contribute to Immune Surveillance

The lingual surface is composed of a tough epithelium that affords effective protection from the resident and food-borne microbiota. The circumvallate taste papillae (CVP) in the back of the tongue are associated with underlying minor salivary glands called von Ebners gland (VEG) that drains its secretions into the trenches of the papillae. The taste buds are exposed to the lingual surface through taste pores, to enable interaction with tastants. These openings may be exploited by pathogens for infection. Mucosa-associated lymphoid tissue (MALT) such as those in the gut epithelium, tonsils and lachrymal and salivary ducts possess specialized cells called microfold (M) cells that transport luminal microbes and present them to underlying immune cells, which then initiate an appropriate immune response. Our previous work indicated that type II taste cells might mediate similar immune surveillance akin to M cells and that CVP is patrolled by large population of immune cells. Using single cell RNASeq (scRNASeq) of CVP, we discovered that the duct cells of the VEG strongly express markers for M cells. The ducts were capable of transcytosing fluorescently labelled E. coli and fluorescent nanobeads, which are then taken up by underlying immune cells. We propose that taste and duct cell-mediated immune surveillance might be crucial for preventing infection of taste papillae and for maintaining taste function, and conversely, this pathway might be hijacked by microbes for infection.

immunology↗