Aster: A New Star in Cholesterol Trafficking
| Autor: | Ajay Chawla, Vassily I. Kutyavin |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cholesterol Endoplasmic reticulum Cell Membrane Proteins Biological Transport Aster (cell biology) Biology Endoplasmic Reticulum Article General Biochemistry Genetics and Molecular Biology Cell biology Cell membrane 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure chemistry Carrier protein medicine Animals lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery |
| Zdroj: | Cell. 175:307-309 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2018.09.025 |
| Popis: | The mechanisms underlying sterol transport in mammalian cells are poorly understood. In particular, how cholesterol internalized from HDL is made available to the cell for storage or modification is unknown. Here we describe three ER-resident proteins (Aster-A, -B, -C) that bind cholesterol and facilitate its removal from the plasma membrane. The crystal structure of the central domain of Aster-A broadly resembles the sterol-binding fold of mammalian StARD proteins, but sequence differences in the Aster pocket result in a distinct mode of ligand binding. The Aster N-terminal GRAM domain binds phosphatidylserine and mediates Aster recruitment to plasma membrane-ER contact sites in response to cholesterol accumulation in the plasma membrane. Mice lacking Aster-B are deficient in adrenal cholesterol ester storage and steroidogenesis due to an inability to transport cholesterol from SR-BI to the ER. These findings identify a nonvesicular pathway for plasma membrane to ER sterol trafficking in mammals. |
| Databáze: | OpenAIRE |
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