Glucose transporter GLUT3: Ontogeny, targeting, and role in the mouse blastocyst

Abstract

The first differentiative event in mammalian development is segregation of the inner cell mass and trophectoderm (TE) lineages. The epithelial TE cells pump f luid into the spherical blastocyst to form the blastocyst cavity. This activity is fuelled by glucose supplied through facilitative glucose transporters. However, the reported kinetic characteristics of blastocyst glucose transport are inconsistent with those of the previously identified transporters and suggested the presence of a high-affinity glucose carrier. We identified and localized the primary transporter in TE cells. It is glucose transporter GLUT3, previously described in the mouse as neuron-specific. In the differentiating embryo, GLUT3 is targeted to the apical membranes of the polarized cells of the compacted morula and then to the apical membranes of TE cells where it has access to maternal glucose. In contrast, GLUT1 was restricted to basolateral membranes of the outer TE cells in both compacted morulae and blastocysts. Using antisense oligodeoxynucleotides to specifically block protein expression, we confirmed that GLUT3 and not GLUT1 is the functional transporter for maternal glucose on the apical TE. More importantly, however, GLUT3 expression is required for blastocyst formation and hence this primary differentiation in mammalian development. This requirement is independent of its function as a glucose transporter because blastocysts will form in the absence of glucose. Thus the vectorial expression of GLUT3 into the apical membrane domains of the outer cells of the morula, which in turn form the TE cells of the blastocyst, is required for blastocyst formation.

The facilitative glucose transporter GLUT3: 20 years of distinction

“…In that report, GLUT1 was purported to be the main glucose transporter, responsible for uptake of maternal glucose. Pantaleon et al (99) noted, however, that this would be unlikely given that the K m of glucose transport was much lower than that of GLUT1. Gardner and Kaye (43) had demonstrated that the mouse blastocyst had a K m of 6.3 Ϯ 0.5 mM for 3-O-methylglucose (3-OMG) whereas GLUT1's K m for 3-OMG is 20.1 Ϯ 2.9 mM.…”

“…Pantaleon et al (99) first described the expression of this transporter in murine embryos in 1997. GLUT1 and GLUT2 had been identified six years earlier in the murine preimplantation embryo (1, 51).…”

Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

“…The different members of the SLC2 family differ in substrate specificity, affinity for cytochalasin B, inhibition by phloretin or phlorizin, and regulation by insulin [11]. Of the 14 SLC2 gene family members, expression of Glut1, Glut2, Glut3, Glut8 and Glut12 (also known as Slc2a1, Slc2a2, Slc2a3, Slc2a8 and Slc2a12) is detected in preimplantation mouse embryos [13][14][15][16][17][18]. GLUT12 protein is not detected in early postimplantation embryos, but it is detected later, during fetal development [17,19].…”

Expression during rat fetal development of GLUT12 – a member of the class III hexose transporter family

“…High levels of GLUT1 and GLUT3 are present in a wide range of fetal tissues, with expression of these transporters greatly decreased after birth in many of these cell types. In the pre-implantation embryo, GLUT3 is the transporter responsible for the uptake of uterine glucose in mice, though GLUT8 may also play a role (Pantaleon et al 1997;Carayannopoulos et al 2000). High levels of GLUT1 protein are also present in pre-implantation embryos, and by day 6.5 to 7.5 glucose is the main substrate consumed (Houghton et al 1996;Pantaleon et al 2001).…”