Genetic link between IRR-receptor and Ly6/PLAUR protein

Abstract

Receptor tyrosine kinase IRR is a pH-sensor that able to be activated by alkaline extracellular media. IRR is a close homologue of the insulin receptor and insulin-like growth factor receptor but no endogenous ligands of a peptide or protein nature have been found for IRR. IRR expression was detected in certain populations of kidney cells, stomach, pancreas and also in parts of the sympathetic and cholinergic neurons. We have previously identified behavioral disorders in mice lacking IRR. In this study we performed a comparative analysis of wild-type mice brain transcriptomes and IRR-knockout mice brain transcriptomes using method of deep sequencing. The most significant difference (two-fold increase in expression) was observed for Ly6/PLAUR protein transcript. It is known that this protein is able to stimulate nicotinic acetylcholine receptor desensibilization. These results suggest that behavioral characteristics of mice lacking IRR are caused by the functional link between IRR and Ly6/PLAUR in cholinergic neurons of the brain.