Sahabandu Natalie, Okada Kyoko, Khan Aisha, Elnatan Daniel, Starr Daniel A, Ori-McKenney Kassandra M, Luxton G W, McKenney Richard J
Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Sci Adv. 2025 Feb 21;11(8):eadq4726. doi: 10.1126/sciadv.adq4726.
Nesprin-2 Giant (N2G) is a large integral membrane protein that physically connects the nucleus to the cytoskeleton, but how N2G performs this activity to maintain nuclear positioning and drive nuclear movement is unclear. This study investigates N2G's role in nucleocytoskeletal coupling, a process critical for cellular function and development. We uncover multiple roles for N2G, including its activity as an F-actin bundler, an adapter that activates kinesin-1 motors, and a mediator of cytoskeletal cross-talk. Notably, N2G directly links kinesin-1 to F-actin, enabling the transport of actin filaments along microtubule tracks, establishing active cross-talk between the actin and microtubule cytoskeletons. These findings provide crucial insights into nuclear movement, advancing our understanding of fundamental cellular processes and their implications in development and disease.
核膜伸展蛋白-2巨蛋白(N2G)是一种大型整合膜蛋白,它在物理上连接细胞核与细胞骨架,但N2G如何执行这一活动以维持核定位并驱动核运动尚不清楚。本研究调查了N2G在核细胞骨架偶联中的作用,这一过程对细胞功能和发育至关重要。我们发现了N2G的多种作用,包括其作为F-肌动蛋白成束蛋白的活性、激活驱动蛋白-1运动蛋白的衔接蛋白以及细胞骨架串扰的介导因子。值得注意的是,N2G直接将驱动蛋白-1与F-肌动蛋白相连,使肌动蛋白丝能够沿微管轨道运输,在肌动蛋白和微管细胞骨架之间建立活跃的串扰。这些发现为核运动提供了关键见解,增进了我们对基本细胞过程及其在发育和疾病中的影响的理解。