Monitoring and Modulating Intracellular Cholesterol Trafficking Using ALOD4, a Cholesterol-Binding Protein

Methods in Molecular Biology
Shreya EndapallyArun Radhakrishnan

Abstract

Mammalian cells carefully control their cholesterol levels by employing multiple feedback mechanisms to regulate synthesis of cholesterol and uptake of cholesterol from circulating lipoproteins. Most of a cell's cholesterol (~80% of total) is in the plasma membrane (PM), but the protein machinery that regulates cellular cholesterol resides in the endoplasmic reticulum (ER) membrane, which contains a very small fraction (~1% of total) of a cell's cholesterol. How does the ER communicate with PM to monitor cholesterol levels in that membrane? Here, we describe a tool, ALOD4, that helps us answer this question. ALOD4 traps cholesterol at the PM, leading to depletion of ER cholesterol without altering total cell cholesterol. The effects of ALOD4 are reversible. This tool has been used to show that the ER is able to continuously sample cholesterol from PM, providing ER with information about levels of PM cholesterol.

Citations

Jun 10, 2020·Nature Immunology·Quan D ZhouSteven J Bensinger
Sep 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Annika KoponenVesa M Olkkonen
Apr 24, 2021·ELife·David W SandersClifford P Brangwynne
Jun 13, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Valentin SchoopDoris Höglinger

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