Cell Biology

Divide and Rule

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Science  18 Apr 2008:
Vol. 320, Issue 5874, pp. 290-291
DOI: 10.1126/science.320.5874.290d

Intracellular cholesterol metabolism is controlled by sterol regulatory element-binding proteins (SREBPs), which are stored in an inactive membrane-bound form within the endoplasmic reticulum (ER) compartment via an interaction with ER-restricted sterol sensors. When the level of cellular sterols is depleted, the sensors let go of the SREBPs, which are then transported to the Golgi complex, where they are cleaved by site-1 protease (S1P). This cleavage liberates the transcription factor domain from the membrane, and it then enters the nucleus and activates the expression of genes involved in sterol and phospholipid metabolism. During inter-phase, like many Golgi proteins, S1P cycles between the ER and the Golgi complex, and when ER and Golgi membranes merge, for example after treatment with the drug brefeldin A, SREBP cleavage is activated. During mitosis, the Golgi disassembles, and some evidence suggests that a fraction of the Golgi and ER membranes merge; so how then can the cell avoid inadvertently activating SREBPs? Bartz et al. show that during mitosis, S1P and SREBP reside in separate compartments: SREBP remains trapped in the ER, and S1P is sequestered in the clustered remnants of the disassembled Golgi. — SMH

EMBO J. 27, 948 (2008).

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