![]() ![]() This membrane is mostly made of fatty molecules known as lipids and about half of these lipids are specifically cholesterol. ![]() At the outer edge of each cell is the plasma membrane, which protects the cell from the external environment. The human body contains trillions of cells. ![]() 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. 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. They then facilitate the transport of this cholesterol via their StART-like domains. ![]() 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. We show that endoplasmic reticulum (ER)-anchored lipid transfer proteins, the GRAMD1s, sense and transport accessible PM cholesterol to the ER. Transition of PM cholesterol between accessible and inaccessible pools maintains cellular homeostasis, but how cells monitor the accessibility of PM cholesterol remains unclear. The majority of PM cholesterol forms complexes with other PM lipids, making it inaccessible for intracellular transport. Cholesterol is a major structural component of the plasma membrane (PM). ![]()
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