Biology subjects

Sukumaran, S. K.

Publications and source records attributed to Sukumaran, S. K..

3 recordsLinked to original sources

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↗

bioRxiv2019

Studying cellular functions in bipolar disorder: Are there specific predictors of lithium response?

BackgroundLithium is the first-line mood stabilizer for the treatment of bipolar disorder (BD). In order to interrogate cellular phenotypes related to disease and lithium treatment response, this study used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs) from BD patients who are well characterized for clinical lithium response.\n\nMethodsBD patients diagnosed according to the DSM-IV criteria; were recruited from the outpatient services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Clinical lithium response was assessed using the \"Alda scale\" and \"NIMH Retrospective Life chart method\". The controls were ethnically matched healthy subjects with no family history of neuropsychiatric illness. NPCs from two BD patients from the same family who clearly differed in their clinical response to lithium were chosen, and compared with healthy population controls. Whole transcriptome sequencing (RNA-Seq) and analysis were performed, with and without in vitro lithium (1mM for 7 days). In addition, mitochondrial membrane potential (MMP), cell viability and cell proliferation parameters were examined. Experiments were also performed in 25 LCLs from BD patients (16 lithium responders and 9 lithium non-responders), and 12 healthy control LCLs, to evaluate them in a system amenable to clinical translation.\n\nResultsRNA-Sequencing and analysis did not reveal differences in NPCs on in vitro lithium treatment. MMP was lower in BD, both in NPCs and LCLs; reversal with in vitro lithium happened only in LCLs and was unrelated to lithium response. Cell proliferation was higher in BD compared to controls, and there was no change on lithium addition. Cell viability assays indicated greater cell death in BD; which could only be rescued in LCLs of clinical lithium responders. The latter finding was associated with enhanced BCL2 and GSK3B expression with in vitro lithium.\n\nDiscussionOverall, our study findings indicate that there are cellular phenotypes related to the disease (mitochondrial potential, cell proliferation) in NPCs and LCLs. We also observed clinical lithium response related phenotypes (cell viability, BCL2/ GSK3B expression) in LCLs. The next step would be to evaluate a larger set of PBMCs from clinical lithium response groups of BD to derive cellular phenotypes related to direct clinical application.

neuroscience↗