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J. Biol. Chem., Vol. 266, Issue 32, 21439-21443, 11, 1991
Y Lange, F Echevarria and TL Steck
Where examined, cholesterol is synthesized in the endoplasmic reticulum;
however, its precursor, zymosterol, is found mostly in the plasma membrane.
The novel implication of these disparate findings is that zymosterol
circulates within the cell. In tracing its movements, we have now
established the following: (a) in human fibroblasts, zymosterol is
converted to cholesterol solely in the rough ER. (b) Little or no
zymosterol or cholesterol accumulates in the rough ER in vivo. (c) Newly
synthesized zymosterol moves to the plasma membrane without a detectable
lag and with a half-time of 9 min, about twice as fast as cholesterol. (d)
The pool of radiolabeled zymosterol in the plasma membrane turns over
rapidly, faster than does intracellular cholesterol. Thus, plasma membrane
zymosterol is not stagnant. (e) [3H]Zymosterol pulsed into intact cells is
initially found in the plasma membrane. It is rapidly internalized and is
then converted to [3H] cholesterol. Half of the [3H]cholesterol produced
returns to the plasma membrane within 30 min of the initial [3H]zymosterol
pulse. (f) Nascent zymosterol accumulates in a buoyant sterol-rich
intracellular membrane before it reaches the plasma membrane. This membrane
also acquires nascent cholesterol, exogenous [3H]zymosterol pulsed into
intact cells, and [3H]cholesterol synthesized from the exogenous [3H]
zymosterol. These results suggest that at least one sterol moves rapidly
and in both directions among the rough endoplasmic reticulum, a sterol-rich
intracellular membrane bearing nascent cholesterol, and the plasma
membrane.
Movement of zymosterol, a precursor of cholesterol, among three membranes in human fibroblasts
Department of Pathology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
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