Science (New York, N.Y.) · 2023
Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Ferrari Alessandra, Whang Emily, Xiao Xu, Kennelly John P, Romartinez-Alonso Beatriz, Mack Julia J, Weston Thomas, Chen Kai, Kim Youngjae, Tol Marcus J, Bideyan Lara, Nguyen Alexander, Gao Yajing, Cui Liujuan, Bedard Alexander H, Sandhu Jaspreet, Lee Stephen D, Fairall Louise, Williams Kevin J, Song Wenxin, Munguia Priscilla, Russell Robert A, Martin Martin G, Jung Michael E, Jiang Haibo, Schwabe John W R, Young Stephen G, Tontonoz Peter
Аннотация
Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes. Loss of NPC1L1 diminishes accessible plasma membrane (PM) cholesterol and abolishes Aster recruitment to the intestinal brush border. Enterocytes lacking Asters accumulate PM cholesterol and show endoplasmic reticulum cholesterol depletion. Aster-deficient mice have impaired cholesterol absorption and are protected against diet-induced hypercholesterolemia. Finally, the Aster pathway can be targeted with a small-molecule inhibitor to manipulate cholesterol uptake. These findings identify the Aster pathway as a physiologically important and pharmacologically tractable node in dietary lipid absorption.