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Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export

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Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. / Heybrock, Saskia; Kanerva, Kristiina; Meng, Ying; Ing, Chris; Liang, Anna; Xiong, Zi-Jian; Weng, Xialian; Ah Kim, Young; Collins, Richard; Trimble, William; Pomès, Régis; Privé, Gilbert G; Annaert, Wim; Schwake, Michael; Heeren, Joerg; Lüllmann-Rauch, Renate; Grinstein, Sergio; Ikonen, Elina; Saftig, Paul; Neculai, Dante.

In: NAT COMMUN, Vol. 10, No. 1, 06.08.2019, p. 3521.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Heybrock, S, Kanerva, K, Meng, Y, Ing, C, Liang, A, Xiong, Z-J, Weng, X, Ah Kim, Y, Collins, R, Trimble, W, Pomès, R, Privé, GG, Annaert, W, Schwake, M, Heeren, J, Lüllmann-Rauch, R, Grinstein, S, Ikonen, E, Saftig, P & Neculai, D 2019, 'Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export', NAT COMMUN, vol. 10, no. 1, pp. 3521. https://doi.org/10.1038/s41467-019-11425-0

APA

Heybrock, S., Kanerva, K., Meng, Y., Ing, C., Liang, A., Xiong, Z-J., Weng, X., Ah Kim, Y., Collins, R., Trimble, W., Pomès, R., Privé, G. G., Annaert, W., Schwake, M., Heeren, J., Lüllmann-Rauch, R., Grinstein, S., Ikonen, E., Saftig, P., & Neculai, D. (2019). Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. NAT COMMUN, 10(1), 3521. https://doi.org/10.1038/s41467-019-11425-0

Vancouver

Heybrock S, Kanerva K, Meng Y, Ing C, Liang A, Xiong Z-J et al. Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. NAT COMMUN. 2019 Aug 6;10(1):3521. https://doi.org/10.1038/s41467-019-11425-0

Bibtex

@article{b780b9b85d1142028b1194b572d10009,
title = "Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export",
abstract = "The intracellular transport of cholesterol is subject to tight regulation. The structure of the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses the molecule and resembles the cavity in SR-B1 that mediates lipid transfer. The detection of cholesterol within the LIMP-2 structure and the formation of cholesterol-like inclusions in LIMP-2 knockout mice suggested the possibility that LIMP2 transports cholesterol in lysosomes. We present results of molecular modeling, crosslinking studies, microscale thermophoresis and cell-based assays that support a role of LIMP-2 in cholesterol transport. We show that the cavity in the luminal domain of LIMP-2 can bind and deliver exogenous cholesterol to the lysosomal membrane and later to lipid droplets. Depletion of LIMP-2 alters SREBP-2-mediated cholesterol regulation, as well as LDL-receptor levels. Our data indicate that LIMP-2 operates in parallel with Niemann Pick (NPC)-proteins, mediating a slower mode of lysosomal cholesterol export.",
keywords = "Animals, CD36 Antigens/genetics, CHO Cells, Carrier Proteins/genetics, Cholesterol, LDL/metabolism, Cricetulus, Fibroblasts, Gene Knockout Techniques, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, Lipid Droplets/metabolism, Lysosome-Associated Membrane Glycoproteins/genetics, Lysosomes/metabolism, Membrane Glycoproteins/genetics, Mice, Protein Domains, RNA, Small Interfering/metabolism, Receptors, Scavenger/genetics",
author = "Saskia Heybrock and Kristiina Kanerva and Ying Meng and Chris Ing and Anna Liang and Zi-Jian Xiong and Xialian Weng and {Ah Kim}, Young and Richard Collins and William Trimble and R{\'e}gis Pom{\`e}s and Priv{\'e}, {Gilbert G} and Wim Annaert and Michael Schwake and Joerg Heeren and Renate L{\"u}llmann-Rauch and Sergio Grinstein and Elina Ikonen and Paul Saftig and Dante Neculai",
year = "2019",
month = aug,
day = "6",
doi = "10.1038/s41467-019-11425-0",
language = "English",
volume = "10",
pages = "3521",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export

AU - Heybrock, Saskia

AU - Kanerva, Kristiina

AU - Meng, Ying

AU - Ing, Chris

AU - Liang, Anna

AU - Xiong, Zi-Jian

AU - Weng, Xialian

AU - Ah Kim, Young

AU - Collins, Richard

AU - Trimble, William

AU - Pomès, Régis

AU - Privé, Gilbert G

AU - Annaert, Wim

AU - Schwake, Michael

AU - Heeren, Joerg

AU - Lüllmann-Rauch, Renate

AU - Grinstein, Sergio

AU - Ikonen, Elina

AU - Saftig, Paul

AU - Neculai, Dante

PY - 2019/8/6

Y1 - 2019/8/6

N2 - The intracellular transport of cholesterol is subject to tight regulation. The structure of the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses the molecule and resembles the cavity in SR-B1 that mediates lipid transfer. The detection of cholesterol within the LIMP-2 structure and the formation of cholesterol-like inclusions in LIMP-2 knockout mice suggested the possibility that LIMP2 transports cholesterol in lysosomes. We present results of molecular modeling, crosslinking studies, microscale thermophoresis and cell-based assays that support a role of LIMP-2 in cholesterol transport. We show that the cavity in the luminal domain of LIMP-2 can bind and deliver exogenous cholesterol to the lysosomal membrane and later to lipid droplets. Depletion of LIMP-2 alters SREBP-2-mediated cholesterol regulation, as well as LDL-receptor levels. Our data indicate that LIMP-2 operates in parallel with Niemann Pick (NPC)-proteins, mediating a slower mode of lysosomal cholesterol export.

AB - The intracellular transport of cholesterol is subject to tight regulation. The structure of the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses the molecule and resembles the cavity in SR-B1 that mediates lipid transfer. The detection of cholesterol within the LIMP-2 structure and the formation of cholesterol-like inclusions in LIMP-2 knockout mice suggested the possibility that LIMP2 transports cholesterol in lysosomes. We present results of molecular modeling, crosslinking studies, microscale thermophoresis and cell-based assays that support a role of LIMP-2 in cholesterol transport. We show that the cavity in the luminal domain of LIMP-2 can bind and deliver exogenous cholesterol to the lysosomal membrane and later to lipid droplets. Depletion of LIMP-2 alters SREBP-2-mediated cholesterol regulation, as well as LDL-receptor levels. Our data indicate that LIMP-2 operates in parallel with Niemann Pick (NPC)-proteins, mediating a slower mode of lysosomal cholesterol export.

KW - Animals

KW - CD36 Antigens/genetics

KW - CHO Cells

KW - Carrier Proteins/genetics

KW - Cholesterol, LDL/metabolism

KW - Cricetulus

KW - Fibroblasts

KW - Gene Knockout Techniques

KW - HeLa Cells

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Lipid Droplets/metabolism

KW - Lysosome-Associated Membrane Glycoproteins/genetics

KW - Lysosomes/metabolism

KW - Membrane Glycoproteins/genetics

KW - Mice

KW - Protein Domains

KW - RNA, Small Interfering/metabolism

KW - Receptors, Scavenger/genetics

U2 - 10.1038/s41467-019-11425-0

DO - 10.1038/s41467-019-11425-0

M3 - SCORING: Journal article

C2 - 31387993

VL - 10

SP - 3521

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -