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A more recent version of this article appeared on February 1, 2004
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Submitted on May 22, 2003
Revised on September 5, 2003
Accepted on October 1, 2003
1 Harvard Medical School
2 Tom A. Rapoport, Ph.D, HHMI/Harvard Medical School, Dept. of Cell Biology, 240 Longwood Avenue, Boston, MA 02115-6091, USA
* Corresponding author. E-mail address: tom rapoport{at}hms.harvard.edu.
The lumen of the endoplasmic reticulum (ER) differs from the
cytosol in its content of ions and other small molecules, but it is
unclear whether the ER membrane is as impermeable as other membranes in
the cell. Here, we have tested the permeability of the ER membrane to
small, nonphysiological molecules. We report that isolated ER vesicles
allow different chemical modification reagents to pass from the outside
into the lumen with little hindrance. In permeabilized cells, the ER
membrane allows the passage of a small, charged modification reagent
that is unable to cross the plasma membrane or the lysosomal and
trans-Golgi membranes. A larger polar reagent of
5
kDa is unable to pass through the ER membrane. Permeation of the small
molecules is passive as it occurs at low temperature in the absence of
energy. These data indicate that the ER membrane is significantly more
leaky than other cellular membranes, a property that may be required
for protein folding and other functions of the ER.
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