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 4 biologically active peptides with varied physiological roles. Alternative splicing of the Calca messenger RNA generates either preprocalcitonin 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-jugular 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.