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Sterols regulate ER‐export dynamics of secretory cargo protein ts‐O45‐G
Author(s) -
Runz Heiko,
Miura Kota,
Weiss Matthias,
Pepperkok Rainer
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601205
Subject(s) - biology , microbiology and biotechnology , dynamics (music) , secretory protein , computational biology , biochemistry , secretion , physics , acoustics
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.