Please use this identifier to cite or link to this item: https://doi.org/10.7554/eLife.51401
Title: Movement of accessible plasma membrane cholesterol by GRAMD1 lipid transfer protein complex
Authors: Naito, T
Ercan, B
Krshnan, L
Triebl, A 
Koh, DHZ
Wei, FY
Tomizawa, K
Torta, FT 
Wenk, MR 
Saheki, Y
Keywords: GRAM domain
StART-like domain
biochemistry
cell biology
chemical biology
cholesterol
human
membrane contact sites
non-vesicular lipid transport
plasma membrane
Amino Acid Sequence
Animals
Biological Transport
COS Cells
Carrier Proteins
Cell Membrane
Chlorocebus aethiops
Cholesterol
Endoplasmic Reticulum
HeLa Cells
Humans
Multiprotein Complexes
Mutant Proteins
Protein Binding
Protein Domains
Sirolimus
Sphingomyelins
Issue Date: 1-Nov-2019
Publisher: eLife Sciences Publications, Ltd
Citation: Naito, T, Ercan, B, Krshnan, L, Triebl, A, Koh, DHZ, Wei, FY, Tomizawa, K, Torta, FT, Wenk, MR, Saheki, Y (2019-11-01). Movement of accessible plasma membrane cholesterol by GRAMD1 lipid transfer protein complex. eLife 8. ScholarBank@NUS Repository. https://doi.org/10.7554/eLife.51401
Abstract: © 2019, eLife Sciences Publications Ltd. All rights reserved. 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 PM cholesterol accessibility 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 one another and populate at ER-PM contacts by sensing a transient expansion of the accessible pool of PM cholesterol via GRAM domains and facilitate its transport via StART-like domains. Cells lacking all three GRAMD1s exhibit striking expansion of the accessible pool of PM cholesterol due to less efficient PM to ER transport of accessible cholesterol. Thus, GRAMD1s facilitate movement of accessible PM cholesterol to the ER in order to counteract acute increase of PM cholesterol, activating non-vesicular cholesterol transport.
Source Title: eLife
URI: https://scholarbank.nus.edu.sg/handle/10635/170366
ISSN: 2050084X
DOI: 10.7554/eLife.51401
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