Sterols regulate ER-export dynamics of secretory cargo protein ts-O45-G.
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.
Runz
Heiko
H
Cell Biology & Cell Biophysics Programme, European Molecular Biology Laboratory, EMBL, Heidelberg, Germany. runz@embl.de
Miura
Kota
K
Weiss
Matthias
M
Pepperkok
Rainer
R
D022181:COP-Coated Vesicles / Q000378:metabolism; D002784:Cholesterol / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
C028391:G protein, vesicular stomatitis virus; C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C512739:SEC23A protein, human; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins; D002784:Cholesterol; C493083:SAR1A protein, human; C513282:SAR1B protein, human; D020559:Monomeric GTP-Binding Proteins