SRC189, a transmembrane protein regulates sensory channel functions

Abstract

Somatic sensation has four major modalities

touch, proprioception, nociception, and temperature sense. These modalities are mediated by distinct pathways to the brain. However, all of these pathways share a common route, dorsal root ganglia (DRG) neurons. Study on the function and mechanism of various ion channels in DRG neurons are currently well established. Yet, unknown mechanisms still remains which need further investigation. Our research group cloned a gene SRC189 that encodes for a transmembrane protein and expected to be highly expressed in DRG neurons but its structure and function is not well known. The aim of this study is to investigate the expression aspects and function of SRC189 in DRG neurons. Tissue distribution of SRC189 was examined by real time quantitative-RT-PCR analysis. As a result, SRC189 was highly expressed in DRG neurons implying the possibility of its role in regulation of sensory transduction. Immunofluorescence images of HEK293T cells were examined for intracellular localization. Heterologous expression of SRC189 showed expression in plasma membrane and partly in golgi apparatus, and was co-localized with tubulin. We investigated the function of protein SRC189 in modulating activities of ion channels in DRG neurons. Surprisingly, protein SRC189 has inhibitory effects on capsaicin evoked intracellular calcium elevation via TRPV1 channels, which are well known nonselective cation channels with essential roles in nociception. However, SRC189 did not affect activities of endothelin receptor A and P2Y2 receptors. We therefore assume that SRC189 regulates calcium influx from extracellular fluid via TRP channels. Our findings demonstrate that transmembrane protein SRC189 highly distributed in DRG neurons is an inhibitory modulator of TRPV1 ion channels. This study provides insights into regulation of sensory channel functions by a novel protein, SRC189.