Institute for Molecular Biology of Barcelona, Spanish Research Council, Barcelona, Spain.
J Cell Biol. 2021 Oct 4;220(10). doi: 10.1083/jcb.202010016. Epub 2021 Jul 20.
Sterols are unevenly distributed within cellular membranes. How their biosynthetic and transport machineries are organized to generate heterogeneity is largely unknown. We previously showed that the yeast sterol transporter Osh2 is recruited to endoplasmic reticulum (ER)-endocytic contacts to facilitate actin polymerization. We now find that a subset of sterol biosynthetic enzymes also localizes at these contacts and interacts with Osh2 and the endocytic machinery. Following the sterol dynamics, we show that Osh2 extracts sterols from these subdomains, which we name ERSESs (ER sterol exit sites). Further, we demonstrate that coupling of the sterol synthesis and transport machineries is required for endocytosis in mother cells, but not in daughters, where plasma membrane loading with accessible sterols and endocytosis are linked to secretion.
甾醇在细胞膜内分布不均匀。其生物合成和运输机制是如何组织起来产生异质性的，在很大程度上还不清楚。我们之前曾表明，酵母甾醇转运蛋白 Osh2 被招募到内质网 (ER)-内吞接触点，以促进肌动蛋白聚合。我们现在发现，一部分甾醇生物合成酶也定位于这些接触点，并与 Osh2 和内吞机制相互作用。我们观察甾醇动态，发现 Osh2 从这些亚域中提取甾醇，我们将这些亚域命名为 ERSESs（ER 甾醇出口位点）。此外，我们证明甾醇合成和运输机制的偶联对于母细胞的内吞作用是必需的，但对于子细胞不是必需的，在子细胞中，质膜与可及甾醇的装载和内吞作用与分泌相联系。
