Transcriptomic analysis of glycan-processing genes in the dorsal root ganglia of diabetic mice and functional characterization on Ca(v)3.2 channels

Ca(v)3.2 T-type calcium channels play an essential role in the transmission of peripheral nociception in the dorsal root ganglia (DRG) and alteration of Ca(v)3.2 expression is associated with the development of peripheral painful diabetic neuropathy (PDN). Several studies have previously documented the role of glycosylation in the expression and functioning of Ca(v)3.2 and suggested that altered glycosylation of the channel may contribute to the aberrant expression of the channel in diabetic conditions. In this study, we aimed to analyze the expression of glycan-processing genes in DRG neurons from a leptin-deficient genetic mouse model of diabetes (db/db). Transcriptomic analysis revealed that several glycan-processing genes encoding for glycosyltransferases and sialic acid-modifying enzymes were upregulated in diabetic conditions. Functional analysis of these enzymes on recombinant Ca(v)3.2 revealed an unexpected loss-of-function of the channel. Collectively, our data indicate that diabetes is associated with an alteration of the glycosylation machinery in DRG neurons. However, individual action of these enzymes when tested on recombinant Ca(v)3.2 cannot explain the observed upregulation of T-type channels under diabetic conditions. Abbreviations: Galnt16: Polypeptide N-acetylgalactosaminyltransferase 16; B3gnt8: UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8; B4galt1: Beta-1,4-galactosyltransferase 1; St6gal1: Beta-galactoside alpha-2,6-sialyltransferase 1; Neu3: Sialidase-3