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

Heybrock S, Kanerva K, Meng Y, Ing C, Liang A, Xiong Z-J, Weng X, Kim YA, Collins R, Trimble W, Pomes R, et al. (2019)
Nature Communications 10: 3521.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
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.
Erscheinungsjahr
2019
Zeitschriftentitel
Nature Communications
Band
10
Art.-Nr.
3521
eISSN
2041-1723
Page URI
https://pub.uni-bielefeld.de/record/2936923

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Heybrock S, Kanerva K, Meng Y, et al. Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. Nature Communications. 2019;10: 3521.
Heybrock, S., Kanerva, K., Meng, Y., Ing, C., Liang, A., Xiong, Z. - J., Weng, X., et al. (2019). Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. Nature Communications, 10, 3521. doi:10.1038/s41467-019-11425-0
Heybrock, S., Kanerva, K., Meng, Y., Ing, C., Liang, A., Xiong, Z. - J., Weng, X., Kim, Y. A., Collins, R., Trimble, W., et al. (2019). Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. Nature Communications 10:3521.
Heybrock, S., et al., 2019. Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. Nature Communications, 10: 3521.
S. Heybrock, et al., “Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export”, Nature Communications, vol. 10, 2019, : 3521.
Heybrock, S., Kanerva, K., Meng, Y., Ing, C., Liang, A., Xiong, Z.-J., Weng, X., Kim, Y.A., Collins, R., Trimble, W., Pomes, R., Prive, G.G., Annaert, W., Schwake, M., Heeren, J., Luellmann-Rauch, R., Grinstein, S., Ikonen, E., Saftig, P., Neculai, D.: Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export. Nature Communications. 10, : 3521 (2019).
Heybrock, Saskia, Kanerva, Kristiina, Meng, Ying, Ing, Chris, Liang, Anna, Xiong, Zi-Jian, Weng, Xialian, Kim, Young Ah, Collins, Richard, Trimble, William, Pomes, Regis, Prive, Gilbert G., Annaert, Wim, Schwake, Michael, Heeren, Joerg, Luellmann-Rauch, Renate, Grinstein, Sergio, Ikonen, Elina, Saftig, Paul, and Neculai, Dante. “Lysosomal integral membrane protein-2 (LIMP-2/SCARB2) is involved in lysosomal cholesterol export”. Nature Communications 10 (2019): 3521.

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