Department of Biochemistry, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.
Université de Paris, CNRS, Institut Jacques Monod, Paris, France.
Nat Cell Biol. 2021 May;23(5):457-466. doi: 10.1038/s41556-021-00677-y. Epub 2021 May 10.
The response of cells to forces is critical for their function and occurs via rearrangement of the actin cytoskeleton. Cytoskeletal remodelling is energetically costly, yet how cells signal for nutrient uptake remains undefined. Here we present evidence that force transmission increases glucose uptake by stimulating glucose transporter 1 (GLUT1). GLUT1 recruitment to and retention at sites of force transmission requires non-muscle myosin IIA-mediated contractility and ankyrin G. Ankyrin G forms a bridge between the force-transducing receptors and GLUT1. This bridge is critical for enabling cells under tension to tune glucose uptake to support remodelling of the actin cytoskeleton and formation of an epithelial barrier. Collectively, these data reveal an unexpected mechanism for how cells under tension take up nutrients and provide insight into how defects in glucose transport and mechanics might be linked.
细胞对力的反应对于其功能至关重要,这种反应是通过肌动球蛋白细胞骨架的重排来实现的。细胞骨架的重塑是能量消耗巨大的,但细胞如何发出信号以摄取营养物质仍未被定义。在这里,我们提出了证据表明,力的传递通过刺激葡萄糖转运蛋白 1(GLUT1)来增加葡萄糖的摄取。GLUT1 募集到力传递部位并保留在那里需要非肌肉肌球蛋白 IIA 介导的收缩和锚蛋白 G。锚蛋白 G 在力转导受体和 GLUT1 之间形成桥梁。这个桥梁对于使处于张力下的细胞能够调节葡萄糖摄取以支持肌动球蛋白细胞骨架的重塑和上皮屏障的形成是至关重要的。总的来说,这些数据揭示了细胞在张力下摄取营养物质的一种意想不到的机制,并为了解葡萄糖转运和力学缺陷如何相关提供了线索。