Presentation Details
| CALCA Gene-Derived Peptide Expression in the Murine Taste System Salin Raj Palayyan, Abdul Hamid Siddiqui, Sunil K Sukumaran. Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA |
Abstract
The Calca mRNA undergoes alternative splicing to generate either preproCGRP or preprocalcitonin. The proteolytic processing of preprocalcitonin generates bioactive peptides - procalcitonin, calcitonin, and katacalcin, while CGRPα is generated from preproCGRP. The cellular origins, processing, and activity of Calca-derived peptides within the taste system remain poorly defined. Previous studies indicated that CGRPα may regulate ATP release from type II taste cells. CGRPα signals via the CGRP1R, while procalcitonin can also bind CGRP1R and antagonize CGRP signaling. We aimed to uncover how Calca gene-derived peptides and CGRP1R signaling are organized within the taste system. Using integrated single-cell and bulk RNA sequencing of murine taste papillae, we uncovered a striking cellular segregation of transcripts for Calca and their receptors. Preprocalcitonin transcripts-but not CGRP-were selectively expressed in Tas1r3+ type II taste cells. In contrast, Calcrl and Ramp1, but not Calcr, were enriched in stem/progenitor and type I taste cells within the circumvallate papillae, as well as in lingual mesenchymal fibroblasts. Analysis of geniculate and nodose-petrosal ganglia revealed robust expression of Cgrp and Cgrp1r subunits, but not procalcitonin or Calcr. The expression validation using qPCR, RNAscope, IHC and western blotting, indicated that procalcitonin but not calcitonin is produced by type II taste cells. These findings reveal a unique distribution of Calca- derived ligands and their receptors in the taste papillae-innervating neurons and resident epithelial cells. We propose that the reciprocal regulation of CGRP1R by CGRPα and procalcitonin may coordinate taste transduction, epithelial regeneration, uncovering new dimensions of neuroepithelial communication in the gustatory system.
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