Karyopherin α2: a control step of glucose-sensitive gene expression in hepatic cells

Abstract

Glucose is required for an efficient expression of the glucose transporter GLUT2 and other genes. We have shown previously that the intracytoplasmic loop of GLUT2 can divert a signal, resulting in the stimulation of glucose-sensitive gene transcription. In the present study, by interaction with the GLUT2 loop, we have cloned the rat karyopherin α2, a receptor involved in nuclear import. The specificity of the binding was restricted to GLUT2, and not GLUT1 or GLUT4, and to karyopherin α2, not α1. When rendered irreversible by a cross-linking agent, this transitory interaction was detected in vivo in hepatocytes. A role for karyopherin α2 in the transcription of two glucose-sensitive genes was investigated by transfection of native and inactive green fluorescent protein—karyopherin α2 in GLUT2-expressing hepatoma cells. The amount of inactive karyopherin α2 receptor reduced, in a dose-dependent manner, the GLUT2 and liver pyruvate kinase mRNA levels by competition with endogenous active receptor. In contrast, the overexpression of karyopherin α2 did not significantly stimulate GLUT2 and liver pyruvate kinase mRNA accumulation in green fluorescent protein-sorted cells. The present study suggests that, in concert with glucose metabolism, karyopherin α2 transmits a signal to the nucleus to regulate glucose-sensitive gene expression. The transitory tethering of karyopherin α2 to GLUT2 at the plasma membrane might indicate that the receptor can load the cargo to be imported locally.