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Insights into the mechanisms of sterol transport between organelles

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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.

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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

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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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  1. Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis and CNRS, 660 Route des lucioles, 06560, Valbonne, France

    Bruno Mesmin, Bruno Antonny & Guillaume Drin

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  1. Bruno Mesmin
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  2. Bruno Antonny
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  3. Guillaume Drin
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Correspondence to Guillaume Drin.

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Mesmin, B., Antonny, B. & Drin, G. Insights into the mechanisms of sterol transport between organelles. Cell. Mol. Life Sci. 70, 3405–3421 (2013). https://doi.org/10.1007/s00018-012-1247-3

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  • DOI: https://doi.org/10.1007/s00018-012-1247-3

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