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

EMBO J. 2006 Jul 12;25(13):2953-65. doi: 10.1038/sj.emboj.7601205. Epub 2006 Jun 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COP-Coated Vesicles / metabolism
  • Cholesterol / physiology*
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / physiology*
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism
  • Kinetics
  • Mannose-Binding Lectins / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism
  • Models, Biological
  • Monomeric GTP-Binding Proteins / metabolism
  • Protein Transport
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Vesicular Transport Proteins / metabolism*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*

Substances

  • G protein, vesicular stomatitis virus
  • LMAN1 protein, human
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • SEC23A protein, human
  • Vesicular Transport Proteins
  • Viral Envelope Proteins
  • Cholesterol
  • SAR1A protein, human
  • SAR1B protein, human
  • Monomeric GTP-Binding Proteins