Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning

Nuno Rocha, Coenraad Kuijl, Rik van der Kant, Lennert Janssen, Diane Houben, Hans Janssen, Wilbert Zwart, Jacques Neefjes

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Late endosomes (LEs) have characteristic intracellular distributions determined by their interactions with various motor proteins. Motor proteins associated to the dynactin subunit p150(Glued) bind to LEs via the Rab7 effector Rab7-interacting lysosomal protein (RILP) in association with the oxysterol-binding protein ORP1L. We found that cholesterol levels in LEs are sensed by ORP1L and are lower in peripheral vesicles. Under low cholesterol conditions, ORP1L conformation induces the formation of endoplasmic reticulum (ER)-LE membrane contact sites. At these sites, the ER protein VAP (VAMP [vesicle-associated membrane protein]-associated ER protein) can interact in trans with the Rab7-RILP complex to remove p150(Glued) and associated motors. LEs then move to the microtubule plus end. Under high cholesterol conditions, as in Niemann-Pick type C disease, this process is prevented, and LEs accumulate at the microtubule minus end as the result of dynein motor activity. These data explain how the ER and cholesterol control the association of LEs with motor proteins and their positioning in cells.

Original languageEnglish
Pages (from-to)1209-25
Number of pages17
JournalJournal of Cell Biology
Volume185
Issue number7
DOIs
Publication statusPublished - 29 Jun 2009
Externally publishedYes

Fingerprint

Endosomes
Endoplasmic Reticulum
Cholesterol
Proteins
Microtubules
Type C Niemann-Pick Disease
R-SNARE Proteins
Dyneins
Dynactin Complex
lysosomal proteins
Motor Activity
Membranes

Keywords

  • Adaptor Proteins, Signal Transducing/genetics
  • Androstenes/metabolism
  • Animals
  • Anticholesteremic Agents/metabolism
  • Carrier Proteins/chemistry
  • Cell Line
  • Cholesterol/metabolism
  • Dynactin Complex
  • Endoplasmic Reticulum/metabolism
  • Endosomes/metabolism
  • Humans
  • Lovastatin/metabolism
  • Microtubule-Associated Proteins/genetics
  • Models, Molecular
  • Niemann-Pick Disease, Type C/metabolism
  • Protein Binding
  • Protein Conformation
  • Receptors, Steroid
  • Recombinant Fusion Proteins/genetics
  • Vesicular Transport Proteins/genetics
  • rab GTP-Binding Proteins/genetics

Cite this

Rocha, Nuno ; Kuijl, Coenraad ; van der Kant, Rik ; Janssen, Lennert ; Houben, Diane ; Janssen, Hans ; Zwart, Wilbert ; Neefjes, Jacques. / Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. In: Journal of Cell Biology. 2009 ; Vol. 185, No. 7. pp. 1209-25.
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title = "Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning",
abstract = "Late endosomes (LEs) have characteristic intracellular distributions determined by their interactions with various motor proteins. Motor proteins associated to the dynactin subunit p150(Glued) bind to LEs via the Rab7 effector Rab7-interacting lysosomal protein (RILP) in association with the oxysterol-binding protein ORP1L. We found that cholesterol levels in LEs are sensed by ORP1L and are lower in peripheral vesicles. Under low cholesterol conditions, ORP1L conformation induces the formation of endoplasmic reticulum (ER)-LE membrane contact sites. At these sites, the ER protein VAP (VAMP [vesicle-associated membrane protein]-associated ER protein) can interact in trans with the Rab7-RILP complex to remove p150(Glued) and associated motors. LEs then move to the microtubule plus end. Under high cholesterol conditions, as in Niemann-Pick type C disease, this process is prevented, and LEs accumulate at the microtubule minus end as the result of dynein motor activity. These data explain how the ER and cholesterol control the association of LEs with motor proteins and their positioning in cells.",
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author = "Nuno Rocha and Coenraad Kuijl and {van der Kant}, Rik and Lennert Janssen and Diane Houben and Hans Janssen and Wilbert Zwart and Jacques Neefjes",
year = "2009",
month = "6",
day = "29",
doi = "10.1083/jcb.200811005",
language = "English",
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Rocha, N, Kuijl, C, van der Kant, R, Janssen, L, Houben, D, Janssen, H, Zwart, W & Neefjes, J 2009, 'Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning' Journal of Cell Biology, vol. 185, no. 7, pp. 1209-25. https://doi.org/10.1083/jcb.200811005

Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. / Rocha, Nuno; Kuijl, Coenraad; van der Kant, Rik; Janssen, Lennert; Houben, Diane; Janssen, Hans; Zwart, Wilbert; Neefjes, Jacques.

In: Journal of Cell Biology, Vol. 185, No. 7, 29.06.2009, p. 1209-25.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning

AU - Rocha, Nuno

AU - Kuijl, Coenraad

AU - van der Kant, Rik

AU - Janssen, Lennert

AU - Houben, Diane

AU - Janssen, Hans

AU - Zwart, Wilbert

AU - Neefjes, Jacques

PY - 2009/6/29

Y1 - 2009/6/29

N2 - Late endosomes (LEs) have characteristic intracellular distributions determined by their interactions with various motor proteins. Motor proteins associated to the dynactin subunit p150(Glued) bind to LEs via the Rab7 effector Rab7-interacting lysosomal protein (RILP) in association with the oxysterol-binding protein ORP1L. We found that cholesterol levels in LEs are sensed by ORP1L and are lower in peripheral vesicles. Under low cholesterol conditions, ORP1L conformation induces the formation of endoplasmic reticulum (ER)-LE membrane contact sites. At these sites, the ER protein VAP (VAMP [vesicle-associated membrane protein]-associated ER protein) can interact in trans with the Rab7-RILP complex to remove p150(Glued) and associated motors. LEs then move to the microtubule plus end. Under high cholesterol conditions, as in Niemann-Pick type C disease, this process is prevented, and LEs accumulate at the microtubule minus end as the result of dynein motor activity. These data explain how the ER and cholesterol control the association of LEs with motor proteins and their positioning in cells.

AB - Late endosomes (LEs) have characteristic intracellular distributions determined by their interactions with various motor proteins. Motor proteins associated to the dynactin subunit p150(Glued) bind to LEs via the Rab7 effector Rab7-interacting lysosomal protein (RILP) in association with the oxysterol-binding protein ORP1L. We found that cholesterol levels in LEs are sensed by ORP1L and are lower in peripheral vesicles. Under low cholesterol conditions, ORP1L conformation induces the formation of endoplasmic reticulum (ER)-LE membrane contact sites. At these sites, the ER protein VAP (VAMP [vesicle-associated membrane protein]-associated ER protein) can interact in trans with the Rab7-RILP complex to remove p150(Glued) and associated motors. LEs then move to the microtubule plus end. Under high cholesterol conditions, as in Niemann-Pick type C disease, this process is prevented, and LEs accumulate at the microtubule minus end as the result of dynein motor activity. These data explain how the ER and cholesterol control the association of LEs with motor proteins and their positioning in cells.

KW - Adaptor Proteins, Signal Transducing/genetics

KW - Androstenes/metabolism

KW - Animals

KW - Anticholesteremic Agents/metabolism

KW - Carrier Proteins/chemistry

KW - Cell Line

KW - Cholesterol/metabolism

KW - Dynactin Complex

KW - Endoplasmic Reticulum/metabolism

KW - Endosomes/metabolism

KW - Humans

KW - Lovastatin/metabolism

KW - Microtubule-Associated Proteins/genetics

KW - Models, Molecular

KW - Niemann-Pick Disease, Type C/metabolism

KW - Protein Binding

KW - Protein Conformation

KW - Receptors, Steroid

KW - Recombinant Fusion Proteins/genetics

KW - Vesicular Transport Proteins/genetics

KW - rab GTP-Binding Proteins/genetics

U2 - 10.1083/jcb.200811005

DO - 10.1083/jcb.200811005

M3 - Article

VL - 185

SP - 1209

EP - 1225

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 7

ER -