Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Laboratory of Regenerative Medicine in Sports Science, School of Sports Science, South China Normal University, Guangzhou, China.
Nat Cell Biol. 2018 Jun;20(6):688-698. doi: 10.1038/s41556-018-0106-3. Epub 2018 May 25.
Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage. Here, we report that α/β-spectrin (β is also called karst) dynamically accumulates and dissolves at the fusogenic synapse between fusing Drosophila muscle cells, where an attacking fusion partner invades its receiving partner with actin-propelled protrusions to promote cell fusion. Using genetics, cell biology, biophysics and mathematical modelling, we demonstrate that spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse. The transiently accumulated spectrin network functions as a cellular fence to restrict the diffusion of cell-adhesion molecules and a cellular sieve to constrict the invasive protrusions, thereby increasing the mechanical tension of the fusogenic synapse to promote cell membrane fusion. Our study reveals a function of spectrin as a mechanoresponsive protein and has general implications for understanding spectrin function in dynamic cellular processes.
血影蛋白是一种膜骨架蛋白，以其在维持细胞形状和保护细胞免受机械损伤方面的结构作用而闻名。在这里，我们报告说，α/β-血影蛋白（β也称为卡斯特）在融合的果蝇肌肉细胞之间的融合突触处动态积累和溶解，在那里，一个攻击性的融合伙伴用肌动蛋白驱动的突起侵入其接受伙伴，以促进细胞融合。通过遗传学、细胞生物学、生物物理学和数学建模，我们证明了血影蛋白在受到剪切变形时表现出一种机械敏感的积累，在融合突触处高度升高。短暂积累的血影蛋白网络作为细胞围栏，限制细胞黏附分子的扩散，并作为细胞筛子，限制侵入性突起，从而增加融合突触的机械张力，促进细胞膜融合。我们的研究揭示了血影蛋白作为一种机械响应蛋白的功能，并对理解血影蛋白在动态细胞过程中的功能具有普遍意义。
