Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9)

Lüscher, Benjamin; Clemençon, Benjamin; Marini, Camilla; Huang, Xiao; Sager, Ruth; Jeanneret, Céline; Reymond, Jean-Louis; Albrecht, Christiane; Hediger, Matthias; Surbek, Daniel; Baumann, Marc Ulrich (January 2014). Placental Uric Acid Transport System: Glucose Transporter 9 (SLC2A9). Reproductive sciences, 21(3), 303A-303A. Sage

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Placental Uric Acid Transport System: Glucose Transporter 9
(SLC2A9).
INTRODUCTION: Pre-eclampsia, a pregnancy-specific disease,
contributes substantially to perinatal morbidity and mortality of both the
mother and her child. Pre-eclampsia is often associated with high maternal
urate serum levels, which in turn has been shown to play a role in the
pathogenesis of this disease. The aim of this study was to investigate the
glucose transporter GLUT9-mediated placental uric acid transport system.
METHODS: In this study western blot, immunofluorescence techniques
as well as a transepithelial transport (Transwell) model were used to
assess GLUT9 protein expression and, respectively, uric acid transport
activity. Electrophysiological techniques and transmission electron
microscopy (TEM) were used to characterize the properties and the
structure of GLUT9.
RESULTS: Uric acid is transported across a BeWo choriocarcinoma cell
monolayer with 530 pmol/min. We could successfully overexpress and
for the first time purify the GLUT9b isoform using the Xenopus laevis
oocytes expression system. Chloride seems to modulate the urate transport
system. TEM revealed that GLUT9b isoform is present as monomer and
dimmer in the Xenopus laevis overexpression model. A class average of
all the particles allowed us to develop a first model of human GLUT9b
structure, which was derived from the published crystal structure of the
bacterial homologue of GLUT1-4.
CONCLUSIONS: In vitro the “materno-fetal” transport of uric acid is
slow indicating that in vivo the fetus might be protected from short-term
fluctuations of maternal urate serum levels. The low-resolution structure
obtained from TEM validates the proposed homology model regarding
the structure of human GLUT9b. In ongoing studies this model is used
to perform virtual screening to identify novel modulators of the urate
transport system enabling the development of novel therapies in pregnancy
complications.

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