Transport of newly synthesized sterol to the sterol-enriched plasma membrane occurs via nonvesicular equilibration. Academic Article uri icon

Overview

MeSH

  • Adenosine Triphosphatases
  • Biological Transport, Active
  • Endoplasmic Reticulum
  • Ergosterol
  • Genes, Fungal
  • Kinetics
  • Models, Biological
  • Mutation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins

MeSH Major

  • Cell Membrane
  • Sterols

abstract

  • The mechanism by which newly synthesized sterols are transported from their site of synthesis, the endoplasmic reticulum (ER), to the sterol-enriched plasma membrane (PM) is not fully understood. Studies in mammalian cells suggest that newly synthesized cholesterol is transported to the PM in Golgi-bypassing vesicles and/or via a nonvesicular process. Using the yeast Saccharomyces cerevisiae as a model system, we now rule out an essential role for known vesicular transport pathways in transporting the major yeast sterol, ergosterol, from its site of synthesis to the PM. We use a cyclodextrin-based sterol capture assay to show that transport of newly synthesized ergosterol to the PM is unaltered in cells defective in Sec18p, a protein required for almost all intracellular vesicular trafficking events; we also show that transport is not blocked in cells that are defective in formation of transport vesicles at the ER or in vesicle fusion with the PM. Our data suggest instead that transport occurs by equilibration (t(1/2) approximately 10-15 min) of ER and PM ergosterol pools via a bidirectional, nonvesicular process that is saturated in wild-type exponentially growing yeast. To reconcile an equilibration process with the high ergosterol concentration of the PM relative to ER, we note that a large fraction of PM ergosterol is found condensed with sphingolipids in membrane rafts that coexist with free sterol. We propose that the concentration of free sterol is similar in the PM and ER and that only free (nonraft) sterol molecules have access to a nonvesicular transport pathway that connects the two organelles. This is the first description of biosynthetic sterol transport in yeast.

publication date

  • April 19, 2005

has subject area

  • Adenosine Triphosphatases
  • Biological Transport, Active
  • Cell Membrane
  • Endoplasmic Reticulum
  • Ergosterol
  • Genes, Fungal
  • Kinetics
  • Models, Biological
  • Mutation
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sterols
  • Vesicular Transport Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1021/bi048296z

PubMed ID

  • 15823040

Additional Document Info

start page

  • 5816

end page

  • 5826

volume

  • 44

number

  • 15