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Sterols regulate ER-export dynamics of secretory cargo protein ts-O45-G Export

The EMBO Journal, Vol. 25, No. 13. (22 June 2006), pp. 2953-2965.

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cholesterol copii er sterol vesicle

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Alterations in endoplasmic reticulum (ER) cholesterol are fundamental for a variety of cellular processes such as the regulation of lipid homeostasis or efficient protein degradation. We show that reduced levels of cellular sterols cause a delayed ER-to-Golgi transport of the secretory cargo membrane protein ts-O45-G and a relocation to the ER of an endogenous protein cycling between the ER and the Golgi complex. Transport inhibition is characterized by a delay in the accumulation of ts-O45-G in ER-exit sites (ERES) and correlates with a reduced mobility of ts-O45-G within ER membranes. A simple mathematical model describing the kinetics of ER-exit predicts that reduced cargo loading to ERES and not the reduced mobility of ts-O45-G accounts for the delayed ER-exit and arrival at the Golgi. Consistent with this, membrane turnover of the COPII component Sec23p is delayed in sterol-depleted cells. Altogether, our results demonstrate the importance of sterol levels in COPII mediated ER-export.


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