Department of Biology, Duke University, Box 90338, Durham, NC 27708, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27708, USA.
Department of Biology, Duke University, Box 90338, Durham, NC 27708, USA.
Dev Cell. 2022 Mar 28;57(6):732-749.e7. doi: 10.1016/j.devcel.2022.02.019. Epub 2022 Mar 21.
Invasive cells use transient, energy-consuming protrusions to breach basement membrane (BM) barriers. Using the ATP sensor PercevalHR during anchor cell (AC) invasion in Caenorhabditis elegans, we show that BM invasion is accompanied by an ATP burst from mitochondria at the invasive front. RNAi screening and visualization of a glucose biosensor identified two glucose transporters, FGT-1 and FGT-2, which bathe invasive front mitochondria with glucose and facilitate the ATP burst to form protrusions. FGT-1 localizes at high levels along the invasive membrane, while FGT-2 is adaptive, enriching most strongly during BM breaching and when FGT-1 is absent. Cytosolic glycolytic enzymes that process glucose for mitochondrial ATP production cluster with invasive front mitochondria and promote higher mitochondrial membrane potential and ATP levels. Finally, we show that UNC-6 (netrin), which polarizes invasive protrusions, also orients FGT-1. These studies reveal a robust and integrated energy acquisition, processing, and delivery network that powers BM breaching.
侵袭细胞利用短暂的、耗能的突起突破基底膜 (BM) 屏障。在秀丽隐杆线虫的锚定细胞 (AC) 侵袭过程中，使用 ATP 传感器 PercevalHR，我们发现 BM 侵袭伴随着来自侵袭前沿线粒体的 ATP 爆发。RNAi 筛选和葡萄糖生物传感器的可视化鉴定出两种葡萄糖转运蛋白，FGT-1 和 FGT-2，它们为侵袭前沿的线粒体提供葡萄糖，并促进 ATP 爆发以形成突起。FGT-1 沿着侵袭膜高水平定位，而 FGT-2 是适应性的，在 BM 突破时和 FGT-1 缺失时最强烈地富集。用于线粒体 ATP 产生的胞质糖酵解酶与侵袭前沿的线粒体聚集，并促进更高的线粒体膜电位和 ATP 水平。最后，我们表明 UNC-6（神经导向因子），它使侵袭突起极化，也使 FGT-1 定向化。这些研究揭示了一个强大而综合的能量获取、处理和传递网络，为 BM 突破提供动力。
