Yc. Feng et al., Overexpression of the inositol phosphatase SopB in human 293 cells stimulates cellular chloride influx and inhibits nuclear mRNA export, P NAS US, 98(3), 2001, pp. 875-879
Citations number
27
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
SopB is an inositol phosphate phosphatase that is a virulence factor in Sal
monella species. We have overexpressed SopB cDNA in a tetracycline-dependen
t systemin human embryonic 293 cells, and used this model system to directl
y analyze the role of SopB in altering inositol metabolite levels in vivo.
Addition of tetracycline to these cells resulted in the rapid induction of
SopB expression, which was coincident with perturbations in the cellular le
vels of multiple soluble inositol phosphates. All of the changes induced by
SopB expression were reversed within 24 h on removal of tetracycline from
media. Specifically, cellular inositol 1,3,4,5,6-pentakisphosphate (InsP(5)
) and inositol hexakisphosphate (InsP(6)) levels were depleted within 4 to
6 h after inducing SopB expression, A transient rise in cellular inositol 1
,4,5,6-tetrakisphosphate was also observed and was accompanied by increased
chloride channel activity. This indicates that SopB alone is sufficient fo
r changes in chloride channel function in cells infected with Salmonella or
ganisms. Depletion of inositol phosphates, including InsP(5) and InsP(6) me
tabolites, was coincident with the accumulation of polyadenylated RNA in th
e nucleus. This suggested that a defect in nuclear export had occurred.More
over, the penetrance of the export defect required localization of SopB to
the nucleus. These results provide evidence that inositol phosphate product
ions may be required for efficient mRNA export in mammalian cells.