Cold exposure induces tyrosine phosphorylation of BIT through NMDA receptors in the rat hypothalamus

Abstract The hypothalamus has a central role in maintaining homeostases of physiological conditions including body temperature and energy balance. To examine molecular responses to cold exposure in the hypothalamus, we examined changes in protein tyrosine phosphorylation in the suprachiasmatic nucleus of the hypothalamus after acute cold exposure in rats. It was found that brain immunoglobulin-like molecule with tyrosine-based inhibitory motifs (BIT, also called SHPS-1, SIRPα or p84), a transmembrane glycoprotein with two ITIM motifs, showed enhanced tyrosine phosphorylation after cold exposure. Its tyrosine phosphorylation induced by cold exposure was also found in other hypothalamic nuclei including the paraventricular nucleus, lateral hypothalamic area, ventromedial hypothalamus, and arcuate nucleus. This phosphorylation was blocked by AP-5, an NMDA receptor antagonist, indicating that it was mediated by NMDA receptors. These results suggest that BIT is involved in the mechanism of neuronal responses to cold exposure in the hypothalamus.