High impact information on SLC2A8

• The discovery of the brain expression of the translocable glucose transporters, GLUT4 then GLUT8, led to the question of their putative role in the central nervous system, particularly in relation to insulin effect [1].
• Some studies suggest a role for GLUT8 in the endoplasmic reticulum stress [1].
• GLUT3 and GLUT8 mRNA are constitutively expressed in chondrocytes and are not regulated by IL-1beta [2].
• Based on homology with GLUT1-5, we have isolated a cDNA for a novel glucose transporter, GLUTX1 [3].
• GLUT8 mRNA was found in testis from adult, but not from prepubertal rats; its expression in human testis was suppressed by estrogen treatment [4].

Biological context of SLC2A8

• 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) [4].
• An expressed sequence tag (STS A005N15) corresponding with the 3'-untranslated region of GLUT8 has previously been mapped to human chromosome 9 [4].
• Thus, our data demonstrate that recruitment of GLUT8 to the endocytic machinery occurs via direct interaction of the dileucine motif with beta2-adaptin, and that endocytosis might be the main site at which GLUT8 is likely to be regulated [5].
• Yeast two-hybrid analyses and GST pulldown assays reveal that the LL signal constitutes a binding site for the beta2-adaptin subunit of the heterotetrameric AP-2 adaptor complex, implicating this motif in targeting of GLUT8 to clathrin-coated vesicles [5].
• We propose that four other sequences obtained from insect genome projects from the honey bee Apis mellifera (ENSAPMP00000006624), the malaria mosquito Anopheles gambiae (EAA11842), and the fruit fly Drosophila melanogaster (AAQ23604 and AAM52591) are likely the orthologues of the fire ant GLUT8 [6].

Anatomical context of SLC2A8

• GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues [3].
• When translated in reticulocytes lysates, GLUTX1 migrates as a 35-kDa protein that becomes glycosylated in the presence of microsomal membranes [3].
• When expressed in Xenopus oocytes, GLUTX1 showed strong transport activity only after suppression of a dileucine internalization motif present in the amino-terminal region [3].
• GLUTX1 mRNA was detected in testis, hypothalamus, cerebellum, brainstem, hippocampus, and adrenal gland [3].
• As a consequence, GLUT8 accumulates at the plasma membrane at comparable levels to those observed in K44A-transfected cells [5].

Other interactions of SLC2A8

• We hypothesize that, in a similar fashion to GLUT4, in vivo cell surface expression of GLUTX1 may be inducible by a hormonal or other stimulus [3].
• Currently, there are five established functional facilitative glucose transporter isoforms (GLUT1-4 and GLUTX1), with GLUT5 being a fructose transporter [7].
• RESULTS: We identified 2 novel genes (GLUT8 and GLUT9) that are members of the facilitative glucose transporter family [8].

Analytical, diagnostic and therapeutic context of SLC2A8

• Western blot analysis of GLUTX1 transiently expressed in HEK293T cells revealed a diffuse band with a molecular mass of 37-50 kDa that could be converted to a approximately 35-kDa polypeptide following enzymatic deglycosylation [3].
• Immunofluorescence microscopy detection of GLUTX1 transfected into HEK293T cells showed an intracellular staining [3].
• Furthermore, immunohistochemistry with antiserum against the C-terminus of GLUT8 indicated that the protein was associated with spermatozoa within the seminiferous and the epididymal tubules [9].

References