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Title: Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex
Authors: Naito, Tomoki
Ercan, Bilge
Krshnan, Logesvaran
Triebl, Alexander
Koh, Dylan Hong Zheng
Wei, Fan-Yan
Tomizawa, Kazuhito
Torta, Federico Tesio
Wenk, Markus R.
Saheki, Yasunori
Keywords: Science::Medicine
Issue Date: 2019
Source: Naito, T., Ercan, B., Krshnan, L., Triebl, A., Koh, D. H. Z., Wei, F.-Y., . . . Saheki, Y. (2019). Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex. eLife, 8, e51401-. doi:10.7554/eLife.51401
Journal: eLife
Abstract: Cholesterol is a major structural component of the plasma membrane (PM). The majority of PM cholesterol forms complexes with other PM lipids, making it inaccessible for intracellular transport. Transition of PM cholesterol between accessible and inaccessible pools maintains cellular homeostasis, but how cells monitor the accessibility of PM cholesterol remains unclear. We show that endoplasmic reticulum (ER)-anchored lipid transfer proteins, the GRAMD1s, sense and transport accessible PM cholesterol to the ER. GRAMD1s bind to one another and populate ER-PM contacts by sensing a transient expansion of the accessible pool of PM cholesterol via their GRAM domains. They then facilitate the transport of this cholesterol via their StART-like domains. Cells that lack all three GRAMD1s exhibit striking expansion of the accessible pool of PM cholesterol as a result of less efficient PM to ER transport of accessible cholesterol. Thus, GRAMD1s facilitate the movement of accessible PM cholesterol to the ER in order to counteract an acute increase of PM cholesterol, thereby activating non-vesicular cholesterol transport.
ISSN: 2050-084X
DOI: 10.7554/eLife.51401
Rights: © 2019 Naito et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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