Karyopherin alpha2: 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 alpha2, a receptor involved in nuclear import. The specificity of the binding was restricted to GLUT2, and not GLUT1 or GLUT4, and to karyopherin alpha2, not alpha1. When rendered irreversible by a cross-linking agent, this transitory interaction was detected in vivo in hepatocytes. A role for karyopherin alpha2 in the transcription of two glucose-sensitive genes was investigated by transfection of native and inactive green fluorescent protein-karyopherin alpha2 in GLUT2-expressing hepatoma cells. The amount of inactive karyopherin alpha2 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 alpha2 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 alpha2 transmits a signal to the nucleus to regulate glucose-sensitive gene expression. The transitory tethering of karyopherin alpha2 to GLUT2 at the plasma membrane might indicate that the receptor can load the cargo to be imported locally.
Authors	Ghislaine Guillemain, Maria J Muñoz-Alonso, Aurélia Cassany, Martine Loizeau, Anne-Marie Faussat, Anne-Françoise Burnol, Armelle Leturque
Journal	The Biochemical journal (Biochem J) Vol. 364 Issue Pt 1 Pg. 201-9 (May 15 2002) ISSN: 0264-6021 [Print] England
PMID	11988093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cross-Linking Reagents Glucose Transporter Type 1 Glucose Transporter Type 2 Glucose Transporter Type 4 Luminescent Proteins Monosaccharide Transport Proteins Muscle Proteins RNA, Messenger Slc2a1 protein, mouse Slc2a1 protein, rat Slc2a4 protein, mouse Slc2a4 protein, rat alpha Karyopherins karyopherin alpha 2 Green Fluorescent Proteins Glucose
Topics	Animals Biological Transport Blotting, Northern Blotting, Western Cloning, Molecular Cross-Linking Reagents (pharmacology) Dose-Response Relationship, Drug Glucose (metabolism) Glucose Transporter Type 1 Glucose Transporter Type 2 Glucose Transporter Type 4 Green Fluorescent Proteins Hepatocytes (metabolism) Liver (cytology, metabolism) Luminescent Proteins (metabolism) Mice Microscopy, Fluorescence Models, Biological Monosaccharide Transport Proteins (metabolism) Muscle Proteins Protein Binding Protein Structure, Tertiary RNA, Messenger (metabolism) Rats Reverse Transcriptase Polymerase Chain Reaction Transcription, Genetic Transfection Tumor Cells, Cultured Two-Hybrid System Techniques alpha Karyopherins (biosynthesis, genetics)

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