Aster Proteins Regulate the Accessible Cholesterol Pool in the Plasma Membrane
| Autor: | Jaspreet S. Sandhu, Cuiwen He, Alessandra Ferrari, Xu Xiao, Peter Tontonoz, John Paul Kennelly, Stephen G. Young, Haibo Jiang, Xun Chi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Secondary Ion
Knockout 1.1 Normal biological development and functioning Spectrometry Mass Secondary Ion Biology Inbred C57BL Endoplasmic Reticulum Medical and Health Sciences 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Bacterial Proteins Underpinning research 3T3-L1 Cells Peritoneal Animals Molecular Biology 030304 developmental biology Mice Knockout 0303 health sciences Gene knockdown Liposome Membrane Glycoproteins Cholesterol Spectrometry Endoplasmic reticulum Macrophages Cell Membrane Transporter Cell Biology Phosphatidylserine Mass Biological Sciences Fibroblasts Sterol Sterol regulatory element-binding protein Cell biology Mice Inbred C57BL chemistry Liposomes Macrophages Peritoneal lipids (amino acids peptides and proteins) Generic health relevance 030217 neurology & neurosurgery Developmental Biology Research Article Sterol Regulatory Element Binding Protein 2 |
| Zdroj: | Mol Cell Biol Molecular and cellular biology, vol 40, iss 19 |
| Popis: | Recent studies have demonstrated the existence of a discrete pool of cholesterol in the plasma membranes (PM) of mammalian cells-referred to as the accessible cholesterol pool-that can be detected by the binding of modified versions of bacterial cytolysins (e.g., anthrolysin O). When the amount of accessible cholesterol in the PM exceeds a threshold level, the excess cholesterol moves to the endoplasmic reticulum (ER), where it regulates the SREBP2 pathway and undergoes esterification. We reported previously that the Aster/Gramd1 family of sterol transporters mediates nonvesicular movement of cholesterol from the PM to the ER in multiple mammalian cell types. Here, we investigated the PM pool of accessible cholesterol in cholesterol-loaded fibroblasts with a knockdown of Aster-A and in mouse macrophages from Aster-B and Aster-A/B-deficient mice. Nanoscale secondary ion mass spectrometry (NanoSIMS) analyses revealed expansion of the accessible cholesterol pool in cells lacking Aster expression. The increased accessible cholesterol pool in the PM was accompanied by reduced cholesterol movement to the ER, evidenced by increased expression of SREBP2-regulated genes. Cosedimentation experiments with liposomes revealed that the Aster-B GRAM domain binds to membranes in a cholesterol concentration-dependent manner and that the binding is facilitated by the presence of phosphatidylserine. These studies revealed that the Aster-mediated nonvesicular cholesterol transport pathway controls levels of accessible cholesterol in the PM, as well as the activity of the SREBP pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|