An Essential Role of Hrs/Vps27 in Endosomal Cholesterol Trafficking

Ximing Du; Abdulla S. Kazim; Andrew J. Brown; Hongyuan Yang

doi:10.1016/j.celrep.2011.10.004

An Essential Role of Hrs/Vps27 in Endosomal Cholesterol Trafficking

Ximing Du, Abdulla S. Kazim, Andrew J. Brown, Hongyuan Yang

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

The endosomal sorting complex required for transport (ESCRT) plays a crucial role in the degradation of ubiquitinated endosomal membrane proteins. Here, we report that Hrs, a key protein of the ESCRT-0 complex, is required for the transport of low-density lipoprotein-derived cholesterol from endosomes to the endoplasmic reticulum. This function of Hrs in cholesterol transport is distinct from its previously defined role in lysosomal sorting and downregulation of membrane receptors via the ESCRT pathway. In line with this, knocking down other ESCRT proteins does not cause prominent endosomal cholesterol accumulation. Importantly, the localization and biochemical properties of key cholesterol-sorting proteins, NPC1 and NPC2, appear to be unchanged upon Hrs knockdown. Our data identify Hrs as a regulator of endosomal cholesterol trafficking and provide additional insights into the budding of intralumenal vesicles.

Original language	English
Pages (from-to)	29-35
Number of pages	7
Journal	Cell Reports
Volume	1
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2011.10.004
Publication status	Published - Jan 26 2012
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2011.10.004

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title = "An Essential Role of Hrs/Vps27 in Endosomal Cholesterol Trafficking",

abstract = "The endosomal sorting complex required for transport (ESCRT) plays a crucial role in the degradation of ubiquitinated endosomal membrane proteins. Here, we report that Hrs, a key protein of the ESCRT-0 complex, is required for the transport of low-density lipoprotein-derived cholesterol from endosomes to the endoplasmic reticulum. This function of Hrs in cholesterol transport is distinct from its previously defined role in lysosomal sorting and downregulation of membrane receptors via the ESCRT pathway. In line with this, knocking down other ESCRT proteins does not cause prominent endosomal cholesterol accumulation. Importantly, the localization and biochemical properties of key cholesterol-sorting proteins, NPC1 and NPC2, appear to be unchanged upon Hrs knockdown. Our data identify Hrs as a regulator of endosomal cholesterol trafficking and provide additional insights into the budding of intralumenal vesicles.",

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An Essential Role of Hrs/Vps27 in Endosomal Cholesterol Trafficking

Abstract

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