TY - JOUR TI - Movement of accessible plasma membrane cholesterol by the GRAMD1 lipid transfer protein complex AU - Naito, Tomoki AU - Ercan, Bilge AU - Krshnan, Logesvaran AU - Triebl, Alexander AU - Koh, Dylan Hong Zheng AU - Wei, Fan-Yan AU - Tomizawa, Kazuhito AU - Torta, Federico Tesio AU - Wenk, Markus R AU - Saheki, Yasunori A2 - Radhakrishnan, Arun A2 - Pfeffer, Suzanne R VL - 8 PY - 2019 DA - 2019/11/14 SP - e51401 C1 - eLife 2019;8:e51401 DO - 10.7554/eLife.51401 UR - https://doi.org/10.7554/eLife.51401 AB - 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. KW - cholesterol KW - GRAM domain KW - membrane contact sites KW - StART-like domain KW - non-vesicular lipid transport KW - plasma membrane JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -