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Cellular and Molecular Life Sciences

, Volume 70, Issue 18, pp 3405–3421 | Cite as

Insights into the mechanisms of sterol transport between organelles

  • Bruno Mesmin
  • Bruno Antonny
  • Guillaume Drin
Review

Abstract

In cells, the levels of sterol vary greatly among organelles. This uneven distribution depends largely on non-vesicular routes of transfer, which are mediated by soluble carriers called lipid-transfer proteins (LTPs). These proteins have a domain with a hydrophobic cavity that accommodates one sterol molecule. However, a demonstration of their role in sterol transport in cells remains difficult. Numerous LTPs also contain membrane-binding elements, but it is not clear how these LTPs couple their ability to target organelles with lipid transport activity. This issue appears critical, since many sterol transporters are thought to act at contact sites between two membrane-bound compartments. Here, we emphasize that biochemical and structural studies provide precious insights into the mode of action of sterol-binding proteins. Recent studies on START, Osh/ORP and NPC proteins suggest models on how these proteins could transport sterol between organelles and, thereby, influence cellular functions.

Keywords

Sterol transport Lipid transfer protein Osh/ORP START 

Abbreviations

DHE

Dehydroergosterol

ER

Endoplasmic reticulum

ERC

Endosomal recycling compartment

FFAT

Two phenylalanines in an acidic tract

LTP

Lipid tranfer protein

LBPA

Lysobisphosphatidic acid

LE/LY 

Late endosome/lysosome

MCD

Methyl-β-cyclodextrin

NPC

Niemann-Pick C

ORP

Oxysterol-binding protein-related protein

ORD

OSBP-related domain

OSBP

Oxysterol-binding protein

Osh

Oxysterol-binding homology protein

PH

Pleckstrin homology

PI

Phosphatidylinositol

PI(4)P

Phosphatidylinositol 4-phosphate

PIP

Phosphatidylinositol phosphate

PM

Plasma membrane

SM

Sphingomyelin

StAR

Steroidogenic acute regulatory protein

START

StAR-related lipid transfer

TGN

trans-Golgi network

Notes

Acknowledgments

We thank Christine Doucet for critical comments on the manuscript. Our work is financed by the ERC (Advanced Grant 268888), the CNRS and the ANR.

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© Springer Basel 2013

Authors and Affiliations

  1. 1.Institut de Pharmacologie Moléculaire et CellulaireUniversité de Nice Sophia-Antipolis and CNRSValbonneFrance

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