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J. Biol. Chem., Vol. 277, Issue 34, 30991-30997, August 23, 2002
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From the Departments of We studied glucose and water passage across wild
type (WT) glucose transporter Glut1 and its T310I pathogenic mutant,
expressing them in Xenopus laevis oocytes. We
found that the T310I mutation produced a 8-fold decrease in glucose
transport (zero-trans influx, 13 ± 2% compared with
WT), accompanied by a 2.8-fold increase in the osmotic water
permeability (Pf 280 ± 40% compared with
WT), and no change in the diffusional water permeability (Pd). The dependence of glucose and water
transports on the amounts of mutant cRNA injected was identical
exponential buildups (k = 19.7 ng), suggesting that
they depend similarly on the quaternary structure. The
Ea values for Pf were 16 ± 0.4 (WT) and 11 ± 1 kcal mol
Changes in Glucose Transport and Water Permeability
Resulting from the T310I Pathogenic Mutation in Glut1 Are Consistent
with Two Transport Channels per Monomer*
§,
,,,**
Ophthalmology,
** Physiology and Cellular Biophysics, and ¶ Neurology,
Columbia University, New York, New York, 10032
1 (T310I). We report
for the first time that 10 mM D-glucose and L-glucose inhibit Pf by ~45% in the
WT but not in the T310I mutant. In addition, 10 mM maltose
reduces Pf (15-20%) in both cases. However, 5 mM L-glucose increased the
Pf of T310I, consistent with a cooperative effect.
These experimental observations and an analysis of our
three-dimensional model strongly suggest the presence of two channels
per Glut1 monomer, one of which can be blocked by the mutation T310I.
*
This work was supported in part by National
Institutes of Health, U. S. Public Health Service Grants EY08918 (to
J. F.), NS01698, NS37949, and RR00645 (to D. C. D.), the Will and
the Colleen Giblin Foundations (to D. C. D.), and Research to Prevent
Blindness, Inc. (to J. F.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a Fight for Sight Fellowship.
To whom correspondence should be addressed: Dept. of
Physiology, College of Physicians & Surgeons, Columbia University, 630 W. 168th St., New York, NY 10032. Tel.: 212-305-9092; Fax:
212-305-2461; E-mail: jf20@columbia.edu.
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