Sterols regulate ER-export dynamics of secretory cargo protein ts-O45-G
Open Access
- 22 June 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 25 (13), 2953-2965
- https://doi.org/10.1038/sj.emboj.7601205
Abstract
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.Keywords
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