GLUT8, a Novel Member of the Sugar Transport Facilitator Family with Glucose Transport Activity

Holger Doege,Annette Schürmann,Gregor Bahrenberg,Andreas Brauers,Hans-Georg Joost

doi:10.1074/jbc.275.21.16275

Abstract

GLUT8 is a novel glucose transporter-like protein that exhibits significant sequence similarity with the members of the sugar transport facilitator family (29.4% of amino acids identical with GLUT1). Human and mouse sequence (86.2% identical amino acids) comprise 12 putative membrane-spanning helices and several conserved motifs (sugar transporter signatures), which have previously been shown to be essential for transport activity, e.g. GRK in loop 2, PETPR in loop 6, QQLSGVN in helix 7, DRAGRR in loop 8, GWGPIPW in helix 10, and PETKG in the C-terminal tail. An expressed sequence tag (STS A005N15) corresponding with the 3'-untranslated region of GLUT8 has previously been mapped to human chromosome 9. COS-7 cells transfected with GLUT8 cDNA expressed a 42-kDa protein exhibiting specific, glucose-inhibitable cytochalasin B binding (K(D) = 56.6 +/- 18 nm) and reconstitutable glucose transport activity (8.1 +/- 1. 4 nmol/(mg protein x 10 s) versus 1.1 +/- 0.1 in control transfections). In human tissues, a 2.4-kilobase pair transcript was predominantly found in testis, but not in testicular carcinoma. Lower amounts of the mRNA were detected in most other tissues including skeletal muscle, heart, small intestine, and brain. GLUT8 mRNA was found in testis from adult, but not from prepubertal rats; its expression in human testis was suppressed by estrogen treatment. It is concluded that GLUT8 is a sugar transport facilitator with glucose transport activity and a hormonally regulated testicular function.

Highlights

Hexose transport into mammalian cells is catalyzed by the members of a small family of 45–55-kDa membrane proteins, GLUT1–GLUT5 (1– 4)
GLUT3 is predominantly expressed in neuronal cells (19), whereas GLUT4 is exclusively found in muscle and adipose tissue (20, 21); its subcellular localization is controlled by insulin (22, 23)
Isolation of Human and Mouse GLUT8 cDNA—In order to identify unknown glucose transporter-like sequences, we performed a search of the EST data bases with the protein sequences of the known GLUT isoforms

Summary

Introduction

Hexose transport into mammalian cells is catalyzed by the members of a small family of 45–55-kDa membrane proteins, GLUT1–GLUT5 (1– 4). Defining characteristics in the family of hexose transporters are the presence of 12 membrane-spanning helices and a number of conserved residues and motifs (see Fig. 3). The known glucose transporter (GLUT)1 isoforms differ in their expression in different tissues, in their kinetic characteristics, i.e. Km values (2), and in their substrate specificity.

Results

Conclusion